MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Trends in Neurosciences' source. Tue, 07 Feb 2012 07:05:49 +0100 http://www.medworm.com/index.php?rid=5659058&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22301434%26dopt%3DAbstract Authors: Jasinska AJ, Lowry CA, Burmeister M Abstract Reports of gene-environment interactions (GxE) between the serotonin transporter gene and stress on risk of depression have generated both excitement and controversy. The controversy persists in part because a mechanistic account of this GxE on serotonergic neurotransmission and risk of depression has been lacking. In this Opinion, we draw on recent discoveries in the functional neuroanatomy of the serotonergic dorsal raphe nucleus (DR) to propose such a mechanistic account. We argue that genetically produced variability in serotonin reuptake during stressor-induced raphe-raphe interactions alters the balance in the amygdala-ventromedial prefrontal cortex (VMPFC)-DR circuitry underlying stressor reactivity and emotion regulation... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5659058 Tue, 31 Jan 2012 05:00:00 +0100 5659058 http://www.medworm.com/index.php?rid=5639981&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22265158%26dopt%3DAbstract Authors: Mandyam CD, Koob GF Abstract Addiction is a chronic relapsing disorder associated with compulsive drug taking, drug seeking and a loss of control in limiting intake, reflected in three stages of a recurrent cycle: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation ("craving"). This review discusses the role of adult-born neural and glial progenitors in drug seeking associated with the different stages of the addiction cycle. A review of the current literature suggests that the loss of newly born progenitors, particularly in hippocampal and cortical regions, plays a role in determining vulnerability to relapse in rodent models of drug addiction. The normalization of drug-impaired neurogenesis or gliogenesis may help reverse neuroplasticity during... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5639981 Wed, 18 Jan 2012 05:00:00 +0100 5639981 http://www.medworm.com/index.php?rid=5601921&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245372%26dopt%3DAbstract Authors: Cullen KE Abstract Understanding how sensory pathways transmit information under natural conditions remains a major goal in neuroscience. The vestibular system plays a vital role in everyday life, contributing to a wide range of functions from reflexes to the highest levels of voluntary behavior. Recent experiments establishing that vestibular (self-motion) processing is inherently multimodal also provide insight into a set of interrelated questions. What neural code is used to represent sensory information in vestibular pathways? How do the interactions between the organism and the environment shape encoding? How is self-motion information processing adjusted to meet the needs of specific tasks? This review highlights progress that has recently been made towards understan... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5601921 Thu, 12 Jan 2012 05:00:00 +0100 5601921 http://www.medworm.com/index.php?rid=5601922&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22240240%26dopt%3DAbstract Authors: Pachernegg S, Strutz-Seebohm N, Hollmann M Abstract The two GluN3 subunits were the last NMDA receptor subunits to be cloned some 15 years ago. Strikingly, despite the steadily growing interest in their function, their physiological role remains elusive. The original billing as dominant-negative modulators of classical NMDA receptors composed of GluN1 and GluN2 subunits has given way to proposals of much more complex functions, including roles in synaptogenesis and synaptic plasticity. In addition, GluN3 subunits in the absence of GluN2 surprisingly assemble with GluN1 into excitatory glycine receptors. This review provides an overview of the unique spatial and temporal expression patterns of the GluN3 subunits, discusses proposed functions and physiological roles for rece... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5601922 Tue, 10 Jan 2012 05:00:00 +0100 5601922 http://www.medworm.com/index.php?rid=5578375&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22222349%26dopt%3DAbstract Authors: Keene AC, Sprecher SG Abstract Understanding how sensory stimuli drive behavior requires a detailed understanding of the molecular and neural nature through which the stimuli are received and processed. The visual system of the fruit fly Drosophila melanogaster shares marked similarities to that of mammals. Although much focus has been given to the fly visual system, an even further simplified eye and brain makes the visual system of Drosophila larvae an excellent model for dissecting sensory processing and behavioral responses to light. Recent work has identified sensory and central brain neurons required for larval visual behaviors, including circadian rhythms. Here, we review the genes and neurons regulating visual processing in Drosophila larvae and discuss the implica... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5578375 Tue, 03 Jan 2012 05:00:00 +0100 5578375 http://www.medworm.com/index.php?rid=5578374&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22222350%26dopt%3DAbstract Authors: Murakoshi H, Yasuda R Abstract Dendritic spines, small bulbous postsynaptic compartments emanating from neuronal dendrites, have been thought to serve as basic units of memory storage. Despite their small size (∼0.1 femtoliter), thousands of species of proteins exist in the spine, including receptors, channels, scaffolding proteins and signaling enzymes. Biochemical signaling mediated by these molecules leads to morphological and functional plasticity of dendritic spines, and ultimately learning and memory in the brain. Here, we review new insights into the mechanisms underlying spine plasticity brought about by recent advances in imaging techniques to monitor molecular events in single dendritic spines. The activity of each protein displays a specific spatiotemporal pat... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5578374 Tue, 03 Jan 2012 05:00:00 +0100 5578374 http://www.medworm.com/index.php?rid=5578373&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22222351%26dopt%3DAbstract Authors: Yaron A, Sprinzak D Abstract Cell-cell communication by juxtacrine signaling plays a key role in the development of the nervous system, from cell fate determination through axonal guidance to synaptogenesis. Interestingly, several juxtacrine signaling systems exhibit an inhibitory interaction between receptors and ligands in the same cell, termed cis inhibition. These include the Notch, semaphorin and ephrin signaling systems. Here we review the role of cis inhibition in these signaling systems in the development of the nervous system. We compare and contrast cis inhibition mechanisms and discuss their potential cellular function as a threshold-generating mechanism. The prevalence of cis inhibition suggests that these interactions and their functional regulatory roles may ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5578373 Tue, 03 Jan 2012 05:00:00 +0100 5578373 http://www.medworm.com/index.php?rid=5578377&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22217451%26dopt%3DAbstract Authors: Schloesser RJ, Martinowich K, Manji HK Abstract Mood-stabilizing drugs are the most widely prescribed pharmacological treatments for bipolar disorder, a disease characterized by recurrent episodes of mania and depression. Despite extensive clinical utilization, significant questions concerning their mechanisms of action remain. In recent years, a diverse set of molecular and cellular targets of these drugs has been identified. Based on these findings, downstream effects on neural and synaptic plasticity within key circuits have been proposed. Here, we discuss recent data, identify current challenges impeding progress and define areas for future investigation. Further understanding of the primary targets and downstream levels of convergence of mood-stabilizing drugs will gu... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5578377 Thu, 22 Dec 2011 05:00:00 +0100 5578377 http://www.medworm.com/index.php?rid=5578376&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22217452%26dopt%3DAbstract Authors: Duman RS, Voleti B Abstract Basic and clinical studies demonstrate that stress and depression are associated with atrophy and loss of neurons and glia, which contribute to the decreased size and function of limbic brain regions that control mood and depression, including the prefrontal cortex and hippocampus. Here, we review findings that suggest that opposing effects of stress and/or depression and antidepressants on neurotrophic factor expression and signaling partly explain these effects. We also discuss recent reports that suggest a possible role for glycogen synthase kinase 3 and upstream wingless (Wnt)-frizzled (Fz) signaling pathways in mood disorders. New studies also demonstrate that the rapid antidepressant actions of NMDA receptor antagonists are associated with... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5578376 Thu, 22 Dec 2011 05:00:00 +0100 5578376 http://www.medworm.com/index.php?rid=5578378&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22217450%26dopt%3DAbstract Authors: Jurd R PMID: 22217450 [PubMed - as supplied by publisher] (Source: Trends in Neurosciences) Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5578378 Wed, 21 Dec 2011 05:00:00 +0100 5578378 http://www.medworm.com/index.php?rid=5550328&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22192173%26dopt%3DAbstract Authors: Pereira JA, Lebrun-Julien F, Suter U Abstract Glial cells and neurons are engaged in a continuous and highly regulated bidirectional dialog. A remarkable example is the control of myelination. Oligodendrocytes in the central nervous system (CNS) and Schwann cells (SCs) in the peripheral nervous system (PNS) wrap their plasma membranes around axons to organize myelinated nerve fibers that allow rapid saltatory conduction. The functionality of this system is critical, as revealed by numerous neurological diseases that result from deregulation of the system, including multiple sclerosis and peripheral neuropathies. In this review we focus on PNS myelination and present a conceptual framework that integrates crucial signaling mechanisms with basic SC biology. We will highlight... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5550328 Tue, 20 Dec 2011 05:00:00 +0100 5550328 http://www.medworm.com/index.php?rid=5535107&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177979%26dopt%3DAbstract Authors: Turecki G, Ernst C, Jollant F, Labonté B, Mechawar N Abstract Suicide and related behaviors are complex phenomena associated with different risk factors. Although most individuals who display suicidal behavior do not have a history of early-life adversity, a significant minority does. Recent animal and human data have suggested that early-life adversity leads to epigenetic regulation of genes involved in stress-response systems. Here, we review this evidence and suggest that early-life adversity increases risk of suicide in susceptible individuals by influencing the development of stable emotional, behavioral and cognitive phenotypes that are likely to result from the epigenetic regulation of the hypothalamic-pituitary-adrenal axis and other systems involved in responses ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5535107 Thu, 15 Dec 2011 05:00:00 +0100 5535107 http://www.medworm.com/index.php?rid=5535106&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177980%26dopt%3DAbstract Authors: Der-Avakian A, Markou A Abstract Anhedonia, or markedly diminished interest or pleasure, is a hallmark symptom of major depression, schizophrenia and other neuropsychiatric disorders. Over the past three decades, the clinical definition of anhedonia has remained relatively unchanged, although cognitive psychology and behavioral neuroscience have expanded our understanding of other reward-related processes. Here, we review the neural bases of the construct of anhedonia that reflects deficits in hedonic capacity and also closely linked to the constructs of reward valuation, decision-making, anticipation and motivation. The neural circuits subserving these reward-related processes include the ventral striatum, prefrontal cortical regions, and afferent and efferent projections... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5535106 Thu, 15 Dec 2011 05:00:00 +0100 5535106 http://www.medworm.com/index.php?rid=5535105&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177981%26dopt%3DAbstract Authors: Arguello PA, Gogos JA Abstract Accumulating evidence indicates substantial etiological and pathophysiological heterogeneity as well as overlap within and across psychiatric disorders. Moreover, it is uncertain at what level, besides gross behavior, mental illnesses can be differentiated. To advance our understanding of psychiatric disease, we advocate a more systematic approach in characterizing a small number of animal models by utilizing unequivocal rare disease mutations and targeted cognitive assessment to identify convergent disease circuits and mechanisms. Based on available data, we discuss the possibility that the temporal dynamics of synaptic plasticity play a central role in disease pathophysiology and that the extent and manner in which they are altered in speci... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5535105 Thu, 15 Dec 2011 05:00:00 +0100 5535105 http://www.medworm.com/index.php?rid=5535108&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177415%26dopt%3DAbstract Authors: Kazmierczak P, Müller U Abstract Animals use acoustic signals to communicate and to obtain information about their environment. The processing of acoustic signals is initiated at auditory sense organs, where mechanosensory hair cells convert sound-induced vibrations into electrical signals. Although the biophysical principles underlying the mechanotransduction process in hair cells have been characterized in much detail over the past 30 years, the molecular building-blocks of the mechanotransduction machinery have proved to be difficult to determine. We review here recent studies that have both identified some of these molecules and established the mechanisms by which they regulate the activity of the still-elusive mechanotransduction channel. PMID: 22177415 [PubMed -... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5535108 Wed, 14 Dec 2011 05:00:00 +0100 5535108 http://www.medworm.com/index.php?rid=5535109&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22169531%26dopt%3DAbstract Authors: Haydar TF, Reeves RH Abstract Trisomy for human chromosome 21 (Hsa21) results in Down syndrome (DS). The finished human genome sequence provides a thorough catalog of the genetic elements whose altered dosage perturbs development and function in DS. However, understanding how small alterations in the steady state transcript levels for <2% of human genes can disrupt development and function of essentially every cell presents a more complicated problem. Mouse models that recapitulate specific aspects of DS have been used to identify changes in brain morphogenesis and function. Here we provide a few examples of how trisomy for specific genes affects the development of the cortex and cerebellum to illustrate how gene dosage effects might contribute to divergence between the... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5535109 Thu, 08 Dec 2011 05:00:00 +0100 5535109 http://www.medworm.com/index.php?rid=5535111&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154068%26dopt%3DAbstract Authors: Lewis DA, Curley AA, Glausier JR, Volk DW Abstract Deficits in cognitive control, a core disturbance of schizophrenia, appear to emerge from impaired prefrontal gamma oscillations. Cortical gamma oscillations require strong inhibitory inputs to pyramidal neurons from the parvalbumin basket cell (PVBC) class of GABAergic neurons. Recent findings indicate that schizophrenia is associated with multiple pre- and postsynaptic abnormalities in PVBCs, each of which weakens their inhibitory control of pyramidal cells. These findings suggest a new model of cortical dysfunction in schizophrenia in which PVBC inhibition is decreased to compensate for an upstream deficit in pyramidal cell excitation. This compensation is thought to rebalance cortical excitation and inhibition, but at ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5535111 Tue, 06 Dec 2011 05:00:00 +0100 5535111 http://www.medworm.com/index.php?rid=5535110&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154154%26dopt%3DAbstract Authors: Hur EM, Saijilafu , Zhou FQ Abstract Axon growth is driven by the movement of a growth cone, a specialized sensory motile structure located at the tip of a growing neurite. Although stalled retraction bulbs have long been recognized as hallmarks of regeneration failure, mechanisms that control the formation and migration of nerve endings are only beginning to be unraveled. Recent studies point to microtubules as key determinants for such processes, and emerging evidence suggests that regulators of actin and microtubule dynamics in the growth cone might serve as attractive targets for controlling both the speed and trajectory of regenerating axons. This review discusses the potential of and recent progress in direct modulation of the growth cone machinery as a novel strateg... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5535110 Mon, 05 Dec 2011 05:00:00 +0100 5535110 http://www.medworm.com/index.php?rid=5475412&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22137336%26dopt%3DAbstract Authors: Smith GM, Falone AE, Frank E Abstract Functional regeneration within the adult spinal cord remains a formidable task. A major barrier to regeneration of sensory axons into the spinal cord is the dorsal root entry zone. This region displays many of the inhibitory features characteristic of other central nervous system injuries. Several experimental treatments, including inactivation of inhibitory molecules (such as Nogo and chondroitin sulfate proteoglycans) or administration of neurotrophic factors (such as nerve growth factor, neurotrophin3, glial-derived neurotrophic factor and artemin), have been found to promote anatomical and functional regeneration across this barrier. However, there have been relatively few experiments to determine whether regenerating axons project... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5475412 Wed, 30 Nov 2011 05:00:00 +0100 5475412 http://www.medworm.com/index.php?rid=5475411&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22137337%26dopt%3DAbstract Authors: Biasini E, Turnbaugh JA, Unterberger U, Harris DA Abstract The presence of the cellular prion protein (PrP(C)) on the cell surface is critical for the neurotoxicity of prions. Although several biological activities have been attributed to PrP(C), a definitive demonstration of its physiological function remains elusive. In this review, we discuss some of the proposed functions of PrP(C), focusing on recently suggested roles in cell adhesion, regulation of ionic currents at the cell membrane and neuroprotection. We also discuss recent evidence supporting the idea that PrP(C) may function as a receptor for soluble oligomers of the amyloid β peptide and possibly other toxic protein aggregates. These data suggest surprising new connections between the physiological function of... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5475411 Wed, 30 Nov 2011 05:00:00 +0100 5475411 http://www.medworm.com/index.php?rid=5475414&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118930%26dopt%3DAbstract Authors: Tronson NC, Corcoran KA, Jovasevic V, Radulovic J Abstract Conditioning and extinction of fear have traditionally been viewed as two independent learning processes for encoding representations of contexts or cues (conditioned stimuli, CS), aversive events (unconditioned stimuli, US), and their relationship. Based on the analysis of protein kinase signaling patterns in neurons of the fear circuit, we propose that fear and extinction are best conceptualized as emotional states triggered by a single CS representation with two opposing values: aversive and non-aversive. These values are conferred by the presence or absence of the US and encoded by distinct sets of kinase signaling pathways and their downstream targets. Modulating specific protein kinases thus has the potential... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5475414 Thu, 24 Nov 2011 05:00:00 +0100 5475414 http://www.medworm.com/index.php?rid=5475413&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22119146%26dopt%3DAbstract Authors: Krook-Magnuson E, Varga C, Lee SH, Soltesz I Abstract Although the diversity of neocortical and hippocampal GABAergic interneurons is recognized in terms of their anatomical, molecular and functional properties, principal cells are usually assumed to constitute homogenous populations. However, even within a single layer, subpopulations of principal cells can often be differentiated by their distinct long-range projection targets. Such subpopulations of principal cells can have different local connection properties and excitatory inputs, forming subnetworks that may serve as separate information-processing channels. Interestingly, as reviewed here, recent evidence has revealed specific instances where interneuron cell types selectively innervated distinct subpopulations of ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5475413 Wed, 23 Nov 2011 05:00:00 +0100 5475413 http://www.medworm.com/index.php?rid=5440005&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22104561%26dopt%3DAbstract Authors: Kral A, Sharma A Abstract Cortical development is dependent on stimulus-driven learning. The absence of sensory input from birth, as occurs in congenital deafness, affects normal growth and connectivity needed to form a functional sensory system, resulting in deficits in oral language learning. Cochlear implants bypass cochlear damage by directly stimulating the auditory nerve and brain, making it possible to avoid many of the deleterious effects of sensory deprivation. Congenitally deaf animals and children who receive implants provide a platform to examine the characteristics of cortical plasticity in the auditory system. In this review, we discuss the existence of time limits for, and mechanistic constraints on, sensitive periods for cochlear implantation and describe t... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5440005 Fri, 18 Nov 2011 05:00:00 +0100 5440005 http://www.medworm.com/index.php?rid=5379865&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22051158%26dopt%3DAbstract Authors: Ohnishi H, Murata Y, Okazawa H, Matozaki T Abstract Src family kinases (SFKs) are non-receptor-type protein tyrosine kinases that were originally identified as the products of proto-oncogenes and were subsequently implicated in the regulation of cell proliferation and differentiation in the developing mammalian brain. Recent studies using transgenic mouse models have demonstrated that SFKs that are highly expressed in the adult brain regulate neuronal plasticity and behavior through tyrosine phosphorylation of key substrates such as neurotransmitter receptors. Here, we provide an overview of these recent studies, as well as discussing how modulation of the endocytosis of neurotransmitter receptors by SFKs contributes, in part, to this regulation. Deregulation of SFK-depend... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5379865 Tue, 01 Nov 2011 04:00:00 +0100 5379865 http://www.medworm.com/index.php?rid=5379867&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018804%26dopt%3DAbstract Authors: Graham RK, Ehrnhoefer DE, Hayden MR Abstract Caspases are cysteine-aspartic proteases that post-translationally modify their substrates through cleavage at specific sites, which causes either substrate inactivation or a gain of function through the generation of active fragments. Currently, each caspase is categorized as either an initiator of apoptosis or an end-stage executioner. Caspase-6 was originally identified as an executioner caspase owing to its role in cleavage of nuclear lamins. However, it has since been shown that caspase-6 cleaves caspases-2, 3 and 8. Furthermore, active caspase-6 is present in post mortem brains of Huntington and Alzheimer disease subjects that do not yet display apoptotic morphology, which suggests a function distinct from its well-validat... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5379867 Fri, 21 Oct 2011 04:00:00 +0100 5379867 http://www.medworm.com/index.php?rid=5379866&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018805%26dopt%3DAbstract Authors: Jenkinson N, Brown P Abstract Synchronised neuronal oscillations at beta frequencies are prevalent in the human motor system, but their function is unclear. In this Opinion article, we propose that the levels of beta oscillations provide a measure of the likelihood that a new voluntary action will need to be actuated. Oscillatory beta activity is in turn modulated by net dopamine levels at sites of cortical input to the basal ganglia. We hypothesise that net dopamine levels are modulated in response to salient internal and external cues. Crucially, the resulting modulation of beta activity is predictive, enabling the appropriate prospective resourcing and preparation of potential actions. Loss of dopamine, as in Parkinson's disease, annuls this function, unless net dopamin... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5379866 Fri, 21 Oct 2011 04:00:00 +0100 5379866 http://www.medworm.com/index.php?rid=5329051&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21999927%26dopt%3DAbstract Authors: Mc Guire C, Beyaert R, van Loo G Abstract Death receptors (DRs) are members of the tumor necrosis factor receptor (TNF-R) superfamily that are characterised by the presence of a conserved intracellular death domain and are able to trigger a signalling pathway leading to apoptosis. Strong evidence suggests that DRs contribute to the pathology of tissue destructive diseases, including multiple sclerosis (MS), the most common inflammatory demyelinating disease of the central nervous system (CNS). Here, we review the evidence supporting a role for DRs in MS pathology and its implications for the development of therapeutic strategies for MS and other demyelinating pathologies of the CNS. PMID: 21999927 [PubMed - as supplied by publisher] (Source: Trends in Neurosciences) Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5329051 Thu, 13 Oct 2011 04:00:00 +0100 5329051 http://www.medworm.com/index.php?rid=5329052&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982585%26dopt%3DAbstract Authors: Yoder RM, Clark BJ, Taube JS Abstract The ability to perceive one's position and directional heading relative to landmarks is necessary for successful navigation within an environment. Recent studies have shown that the visual system dominantly controls the neural representations of directional heading and location when familiar visual cues are available, and several neural circuits, or streams, have been proposed to be crucial for visual information processing. Here, we summarize the evidence that the dorsal presubiculum (also known as the postsubiculum) is critically important for the direct transfer of visual landmark information to spatial signals within the limbic system. PMID: 21982585 [PubMed - as supplied by publisher] (Source: Trends in Neurosciences) Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5329052 Thu, 06 Oct 2011 04:00:00 +0100 5329052 http://www.medworm.com/index.php?rid=5281121&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21943493%26dopt%3DAbstract Authors: Jurd R PMID: 21943493 [PubMed - in process] (Source: Trends in Neurosciences) Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5281121 Sat, 01 Oct 2011 04:00:00 +0100 5281121 http://www.medworm.com/index.php?rid=5231483&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21917323%26dopt%3DAbstract Authors: Soltesz I Abstract The Grete Lundbeck European Brain Research Foundation awarded the inaugural Brain Prize 2011 to Péter Somogyi, Tamás Freund and György Buzsáki 'for their wide-ranging, technically and conceptually brilliant research on the functional organization of neuronal circuits in the cerebral cortex, especially in the hippocampus, a region that is crucial for certain forms of memory'. The present article highlights key findings and major conceptual contributions by these three scientists that were recognized by the award. PMID: 21917323 [PubMed - as supplied by publisher] (Source: Trends in Neurosciences) Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5231483 Mon, 12 Sep 2011 04:00:00 +0100 5231483 http://www.medworm.com/index.php?rid=5219101&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21889806%26dopt%3DAbstract Authors: Pennartz CM, Ito R, Verschure PF, Battaglia FP, Robbins TW Abstract The hippocampal formation and striatum subserve declarative and procedural memory, respectively. However, experimental evidence suggests that the ventral striatum, as opposed to the dorsal striatum, does not lend itself to being part of either system. Instead, it may constitute a system integrating inputs from the amygdala, prefrontal cortex and hippocampus to generate motivational, outcome-predicting signals that invigorate goal-directed behaviors. Inspired by reinforcement learning models, we suggest an alternative scheme for computational functions of the striatum. Dorsal and ventral striatum are proposed to compute outcome predictions largely in parallel, using different types of information as input. ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5219101 Thu, 01 Sep 2011 04:00:00 +0100 5219101 http://www.medworm.com/index.php?rid=5192991&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21880379%26dopt%3DAbstract Authors: Jones MW, McHugh TJ Abstract The hippocampus integrates the encoding, storage and recall of memories, binding the spatio-temporal and sensory information that constitutes experience and keeping episodes in their correct context. The rapid and accurate processing of such daunting volumes of continuously changing data relies on dynamically assigning different aspects of mnemonic processing to specialized, interconnected networks corresponding to the anatomical subfields of dentate gyrus (DG), CA3 and CA1. However, differentially processed information ultimately has to be reintegrated into conjunctive representations, and this is unlikely to be achieved by unidirectional, sequential steps through a DG-CA3-CA1 loop. In this Review, we highlight recently discovered anatomical a... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5192991 Sun, 28 Aug 2011 23:00:00 +0100 5192991 http://www.medworm.com/index.php?rid=5176467&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21872944%26dopt%3DAbstract Authors: Wei W, Feller MB Abstract The direction-selective circuit in the retina extracts the directional information of image motion in the visual scene. It is a classic model for neural circuit analysis because its input and output are well-defined and accessible to physiological measurements. However, the neural basis of direction selectivity is still not fully understood. Indeed, this ostensibly simple computation arises from a collection of complex neural mechanisms at all levels of circuit organization. In this review, we describe recent advances in genetic, imaging and optogenetic techniques that have improved our understanding of the synaptic organization and development underlying retinal direction selectivity. PMID: 21872944 [PubMed - as supplied by publisher] (Source... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5176467 Thu, 25 Aug 2011 23:00:00 +0100 5176467 http://www.medworm.com/index.php?rid=5157406&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21851992%26dopt%3DAbstract Authors: Lisman J, Grace AA, Duzel E Abstract According to the Hebb rule, the change in the strength of a synapse depends only on the local interaction of presynaptic and postsynaptic events. Studies at many types of synapses indicate that the early phase of long-term potentiation (LTP) has Hebbian properties. However, it is now clear that the Hebb rule does not account for late LTP; this requires an additional signal that is non-local. For novel information and motivational events such as rewards this signal at hippocampal CA1 synapses is mediated by the neuromodulator, dopamine. In this Review we discuss recent experimental findings that support the view that this 'neoHebbian' framework can account for memory behavior in a variety of learning situations. PMID: 21851992 [PubMe... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5157406 Mon, 15 Aug 2011 23:00:00 +0100 5157406 http://www.medworm.com/index.php?rid=5141522&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840610%26dopt%3DAbstract Authors: Hall DH, Treinin M Abstract Sensory dendrites fall into many different morphological and functional classes. Polymodal nociceptors are one subclass of sensory neurons, which are of particular note owing to their elaborate dendritic arbors. Complex developmental programs are required to form these arbors and there is striking conservation of morphology, function and molecular determinants between vertebrate and invertebrate polymodal nociceptors. Based on these studies, we argue that arbor morphology plays an important role in the function of polymodal nociceptors. Similar associations between form and function might explain the plethora of dendrite morphologies seen among all sensory neurons. PMID: 21840610 [PubMed - as supplied by publisher] (Source: Trends in Neurosc... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5141522 Thu, 11 Aug 2011 23:00:00 +0100 5141522 http://www.medworm.com/index.php?rid=5141524&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840068%26dopt%3DAbstract Authors: Wang G, Grone B, Colas D, Appelbaum L, Mourrain P Abstract Sleep is a fundamental and evolutionarily conserved aspect of animal life. Recent studies have shed light on the role of sleep in synaptic plasticity. Demonstrations of memory replay and synapse homeostasis suggest that one essential role of sleep is in the consolidation and optimization of synaptic circuits to retain salient memory traces despite the noise of daily experience. Here, we review this recent evidence and suggest that sleep creates a heightened state of plasticity, which may be essential for this optimization. Furthermore, we discuss how sleep deficits seen in diseases such as Alzheimer's disease and autism spectrum disorders might not just reflect underlying circuit malfunction, but could also play a ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5141524 Wed, 10 Aug 2011 23:00:00 +0100 5141524 http://www.medworm.com/index.php?rid=5141523&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840069%26dopt%3DAbstract Authors: Huberman AD, Niell CM Abstract Understanding the neural basis of visual perception is a long-standing fundamental goal of neuroscience. Historically, most vision studies were carried out on humans, macaques and cats. Over the past 5 years, however, a growing number of researchers have begun using mice to parse the mechanisms underlying visual processing; the rationale is that, despite having relatively poor acuity, mice are unmatched in terms of the variety and sophistication of tools available to label, monitor and manipulate specific cell types and circuits. In this review, we discuss recent advances in understanding the mouse visual system at the anatomical, receptive field and perceptual level, focusing on the opportunities and constraints those features provide toward... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5141523 Wed, 10 Aug 2011 23:00:00 +0100 5141523 http://www.medworm.com/index.php?rid=5141525&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21831459%26dopt%3DAbstract Authors: Walter AM, Groffen AJ, Sørensen JB, Verhage M Abstract Regulated neurotransmitter secretion depends on Ca(2+) sensors, C2 domain proteins that associate with phospholipids and soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE) complexes to trigger release upon Ca(2+) binding. Ca(2+) sensors are thought to prevent spontaneous fusion at rest (clamping) and to promote fusion upon Ca(2+) activation. At least eight, often coexpressed, Ca(2+) sensors have been identified in mammals. Accumulating evidence suggests that multiple Ca(2+) sensors interact, rather than work autonomously, to produce the complex secretory response observed in neurons and secretory cells. In this review, we present several working models to describe how different sensors might... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5141525 Sun, 07 Aug 2011 23:00:00 +0100 5141525 http://www.medworm.com/index.php?rid=5103716&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21816493%26dopt%3DAbstract Authors: Schmidt TM, Chen SK, Hattar S For decades, rods and cones were thought to be the only photoreceptors in the mammalian retina. However, a population of atypical photoreceptive retinal ganglion cells (RGCs) expresses the photopigment melanopsin and is intrinsically photosensitive (ipRGCs). These ipRGCs are crucial for relaying light information from the retina to the brain to control circadian photoentrainment, pupillary light reflex, and sleep. ipRGCs were initially described as a uniform population involved solely in signaling irradiance for non-image forming functions. Recent work, however, has uncovered that ipRGCs are unexpectedly diverse at the molecular, cellular and functional levels, and could even be involved in image formation. This review summarizes our current under... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5103716 Mon, 01 Aug 2011 23:00:00 +0100 5103716 http://www.medworm.com/index.php?rid=5103717&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21798604%26dopt%3DAbstract Authors: Mahan AL, Ressler KJ Posttraumatic stress disorder (PTSD) is an anxiety disorder that can develop after a traumatic experience such as domestic violence, natural disasters or combat-related trauma. The cost of such disorders on society and the individual can be tremendous. In this article, we review how the neural circuitry implicated in PTSD in humans is related to the neural circuitry of fear. We then discuss how fear conditioning is a suitable model for studying the molecular mechanisms of the fear components that underlie PTSD, and the biology of fear conditioning with a particular focus on the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB), GABAergic and glutamatergic ligand-receptor systems. We then summarize how such approaches might help to inform ou... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5103717 Mon, 25 Jul 2011 23:00:00 +0100 5103717 http://www.medworm.com/index.php?rid=5103718&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21788086%26dopt%3DAbstract Authors: Yassa MA, Stark CE The ability to discriminate among similar experiences is a crucial feature of episodic memory. This ability has long been hypothesized to require the hippocampus, and computational models suggest that it is dependent on pattern separation. However, empirical data for the role of the hippocampus in pattern separation have not been available until recently. This review summarizes data from electrophysiological recordings, lesion studies, immediate-early gene imaging, transgenic mouse models, as well as human functional neuroimaging, that provide convergent evidence for the involvement of particular hippocampal subfields in this key process. We discuss the impact of aging and adult neurogenesis on pattern separation, and also highlight several challenges to lin... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5103718 Fri, 22 Jul 2011 23:00:00 +0100 5103718 http://www.medworm.com/index.php?rid=5057638&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21774998%26dopt%3DAbstract Authors: Valenza M, Cattaneo E Recent findings suggest that alterations in cholesterol homeostasis might be associated with Huntington's disease (HD). Although alterations in cholesterol content have been detected in cell models and several rodent models of HD, it is currently unclear what the potential mechanisms underlying cholesterol perturbations are. Furthermore, it remains to be determined whether these observed changes in cholesterol homeostasis are involved in the pathogenesis of HD or occur as a secondary event. In this review, we provide an overview of current studies that have begun to address these issues and discuss recent findings suggesting that normal huntingtin protein might participate in regulating cholesterol biosynthesis. A better understanding of how alterations i... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5057638 Sun, 17 Jul 2011 23:00:00 +0100 5057638 http://www.medworm.com/index.php?rid=5057640&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21764143%26dopt%3DAbstract Authors: Pickens CL, Airavaara M, Theberge F, Fanous S, Hope BT, Shaham Y It was suggested in 1986 that cue-induced drug craving in cocaine addicts progressively increases over the first several weeks of abstinence and remains high for extended periods. During the past decade, investigators have identified an analogous incubation phenomenon in rodents, in which time-dependent increases in cue-induced drug seeking are observed after withdrawal from intravenous cocaine self-administration. Such an incubation of drug craving is not specific to cocaine, as similar findings have been observed after self-administration of heroin, nicotine, methamphetamine and alcohol in rats. In this review, we discuss recent results that have identified important brain regions involved in the incubation of ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5057640 Thu, 14 Jul 2011 23:00:00 +0100 5057640 http://www.medworm.com/index.php?rid=5057642&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21742388%26dopt%3DAbstract Authors: Krieglstein K, Zheng F, Unsicker K, Alzheimer C It is becoming increasingly clear that members of the transforming growth factor-β (TGF-β) family have roles in the central nervous system that extend beyond their well-established roles as neurotrophic and neuroprotective factors. Recent findings have indicated that the TGF-β signaling pathways are involved in the modulation of both excitatory and inhibitory synaptic transmission in the adult mammalian brain. In this review, we discuss how TGF-β, bone morphogenetic protein and activin signaling at central synapses modulate synaptic plasticity, cognition and affective behavior. We also discuss the implications of these findings for the molecular understanding and potential treatment of neuropsychiatric diseases, such as anxie... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5057642 Thu, 07 Jul 2011 23:00:00 +0100 5057642 http://www.medworm.com/index.php?rid=5057641&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21742389%26dopt%3DAbstract Authors: Mednick SC, Cai DJ, Shuman T, Anagnostaras S, Wixted JT Memories are often classified as hippocampus dependent or independent, and sleep has been found to facilitate both, but in different ways. In this Opinion, we explore the optimal neural state for cellular and systems consolidation of hippocampus-dependent memories that benefit from sleep. We suggest that these two kinds of consolidation, which are ordinarily treated separately, overlap in time and jointly benefit from a period of reduced interference (during which no new memories are formed). Conditions that result in reduced interference include slow wave sleep (SWS), NMDA receptor antagonists, benzodiazepines, alcohol and acetylcholine antagonists. We hypothesize that the consolidation of hippocampal-dependent memories ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5057641 Thu, 07 Jul 2011 23:00:00 +0100 5057641 http://www.medworm.com/index.php?rid=5057643&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741098%26dopt%3DAbstract Authors: Stys PK Axons have evolved to acquire myelination, enabling denser packing and speedier transmission. Although myelin is considered a passive insulator, recent reports suggest a more dynamic role. Axons, in turn, are endowed with neurotransmitter release and uptake systems along their trunks. Based on these observations, I argue that there may exist a new type of chemical synapse between axon and myelin, one that supports activity-dependent communication between the two. This raises intriguing possibilities of dynamic fine-tuning of the myelin sheath even in adulthood, efficient recruitment of resources for myelin maintenance and bi-directional signaling, whereby the axon informs its myelinating cell of its metabolic needs proportionally to the electrical traffic it is transmi... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5057643 Tue, 05 Jul 2011 23:00:00 +0100 5057643 http://www.medworm.com/index.php?rid=5008994&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723623%26dopt%3DAbstract Authors: Schultz ML, Tecedor L, Chang M, Davidson BL Lysosomal storage diseases (LSDs) are a class of metabolic disorders caused by mutations in proteins critical for lysosomal function. Such proteins include lysosomal enzymes, lysosomal integral membrane proteins, and proteins involved in the post-translational modification and trafficking of lysosomal proteins. There are many recognized forms of LSDs and, although individually rare, their combined prevalence is estimated to be 1 in 8000 births. Over two-thirds of LSDs involve central nervous system (CNS) dysfunction (progressive cognitive and motor decline) and these symptoms are often the most debilitating. Although the genetic basis for these disorders is clear and the biochemistry of the proteins well understood, the cellular mech... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5008994 Wed, 29 Jun 2011 23:00:00 +0100 5008994 http://www.medworm.com/index.php?rid=5008995&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21704388%26dopt%3DAbstract Authors: Todi SV, Paulson HL Many pathways important to the nervous system are regulated by the post-translational conjugation of ubiquitin to target proteins. The reversal of ubiquitination, or deubiquitination, is equally critical to neuronal function. By countering protein ubiquitination, deubiquitinating enzymes (DUBs) help control neuronal fate determination, axonal pathfinding and synaptic communication and plasticity. The significance of DUBs to the nervous system is underscored by links to various neurological diseases. Owing to cell type or substrate specificity, certain DUBs might also represent therapeutic targets for neurodegeneration. Here, we review recent findings that have shaped our current understanding of emerging functions for DUB in the nervous system. PMID: 21... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5008995 Thu, 23 Jun 2011 23:00:00 +0100 5008995 http://www.medworm.com/index.php?rid=5008996&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21700347%26dopt%3DAbstract Authors: Dormann D, Haass C Misfolded TAR DNA binding protein 43 (TDP-43) and Fused-In-Sarcoma (FUS) protein have recently been identified as pathological hallmarks of the neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) characterized by the presence of ubiquitin-positive inclusions (FTLD-U). Although TDP-43 and FUS are normally located predominantly in the nucleus, pathological TDP-43 and FUS inclusions are mostly found in the cytosol. Cytosolic deposition is paralleled by a striking nuclear depletion of either protein. Based on a number of recent findings, we postulate that defects in nuclear import are an important step towards TDP-43 and FUS dysfunction. Failure of nuclear transport can arise from mutations within a nuclea... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5008996 Mon, 20 Jun 2011 23:00:00 +0100 5008996 http://www.medworm.com/index.php?rid=5008998&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21696833%26dopt%3DAbstract Authors: Dani JA, Balfour DJ Although the addictive influence of tobacco was recognized very early, the modern concepts of nicotine addiction have relied on knowledge of cholinergic neurotransmission and nicotinic acetylcholine receptors (nAChRs). The discovery of the 'receptive substance' by Langley, that would turn out to be nAChRs, and 'Vagusstoff' (acetylcholine) by Loewi, coincided with an exciting time when the concept of chemical synaptic transmission was being formulated. More recently, the application of more powerful techniques and the study of animal models that replicate key features of nicotine dependence have led to important advancements in our understanding of molecular, cellular and systems mechanisms of nicotine addiction. In this review, we present a historical persp... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5008998 Sun, 19 Jun 2011 23:00:00 +0100 5008998 http://www.medworm.com/index.php?rid=5008997&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21696834%26dopt%3DAbstract Authors: Ewers M, Sperling RA, Klunk WE, Weiner MW, Hampel H Alzheimer's disease (AD) is a progressive age-related neurodegenerative disease. At the time of clinical manifestation of dementia, significant irreversible brain damage is already present, rendering the diagnosis of AD at early stages of the disease an urgent prerequisite for therapeutic treatment to halt, or at least slow, disease progression. In this review, we discuss various neuroimaging measures that are proving to have potential value as biomarkers of AD pathology for the detection and prediction of AD before the onset of dementia. Recent studies that have identified AD-like structural and functional brain changes in elderly people who are cognitively within the normal range or who have mild cognitive impairment (MCI) ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=5008997 Sun, 19 Jun 2011 23:00:00 +0100 5008997 http://www.medworm.com/index.php?rid=4961450&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21665298%26dopt%3DAbstract Authors: Mohawk JA, Takahashi JS The suprachiasmatic nucleus (SCN) of the hypothalamus is the site of the master circadian pacemaker in mammals. The individual cells of the SCN are capable of functioning independently from one another and therefore must form a cohesive circadian network through intercellular coupling. The network properties of the SCN lead to coordination of circadian rhythms among its neurons and neuronal subpopulations. There is increasing evidence for multiple interconnected oscillators within the SCN, and in this review we will highlight recent advances in our knowledge of the complex organization and function of the cellular and network-level SCN clock. Understanding the way in which synchrony is achieved between cells in the SCN will provide insight into the mean... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4961450 Thu, 09 Jun 2011 23:00:00 +0100 4961450 http://www.medworm.com/index.php?rid=4865785&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21596448%26dopt%3DAbstract Authors: Waites CL, Garner CC Neurons communicate with one another at specialized contact sites called synapses, composed of pre- and postsynaptic compartments. Presynaptic compartments, or 'boutons', signal to the postsynaptic compartment by releasing chemical neurotransmitter in response to incoming electrical impulses. Recent studies link defects in the function of presynaptic boutons to the etiology of several neurodevelopmental and neurodegenerative diseases, including autism, schizophrenia and Alzheimer's disease. In this review, we describe five core functions of presynaptic boutons and the molecules that mediate these functions, focusing on a subset that are linked to human disease. We also discuss potential mechanisms through which the loss or alteration of these specific mole... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4865785 Mon, 16 May 2011 23:00:00 +0100 4865785 http://www.medworm.com/index.php?rid=4865786&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592595%26dopt%3DAbstract Authors: Mabb AM, Judson MC, Zylka MJ, Philpot BD Angelman syndrome (AS) is a severe genetic disorder caused by mutations or deletions of the maternally inherited UBE3A gene. UBE3A encodes an E3 ubiquitin ligase that is expressed biallelically in most tissues but is maternally expressed in almost all neurons. In this review, we describe recent advances in understanding the expression and function of UBE3A in the brain and the etiology of AS. We highlight current AS model systems, epigenetic mechanisms of UBE3A regulation, and the identification of potential UBE3A substrates in the brain. In the process, we identify major gaps in our knowledge that, if bridged, could move us closer to identifying treatments for this debilitating neurodevelopmental disorder. PMID: 21592595 [PubMed - ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4865786 Sun, 15 May 2011 23:00:00 +0100 4865786 http://www.medworm.com/index.php?rid=4812640&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21549434%26dopt%3DAbstract Authors: McNally GP, Johansen JP, Blair HT Pavlovian fear conditioning depends on synaptic plasticity at amygdala neurons. Here, we review recent electrophysiological, molecular and behavioral evidence suggesting the existence of a distributed neural circuitry regulating amygdala synaptic plasticity during fear learning. This circuitry, which involves projections from the midbrain periaqueductal gray region, can be linked to prediction error and expectation modulation of fear learning, as described by associative and computational learning models. It controls whether, and how much, fear learning occurs by signaling aversive events when they are unexpected. Functional neuroimaging and clinical studies indicate that this prediction circuit is recruited in humans during fear learning and ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4812640 Wed, 04 May 2011 23:00:00 +0100 4812640 http://www.medworm.com/index.php?rid=4812641&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21507493%26dopt%3DAbstract Authors: Alger BE, Kim J The endocannabinoid system consists of G-protein-coupled cannabinoid receptors that can be activated by cannabis-derived drugs and small lipids termed endocannabinoids (eCBs) plus associated biochemical machinery (precursors, synthetic and degradative enzymes, transporters). The eCB system in the brain primarily influences neuronal synaptic communication, and affects biological functions - including eating, anxiety, learning and memory, growth and development - via an array of actions throughout the nervous system. Although many aspects of synaptic regulation by eCBs are becoming clear, details of the subcellular organization and regulation of the eCB system are less well understood. This review focuses on recent investigations that illuminate fundamental issue... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4812641 Sun, 17 Apr 2011 23:00:00 +0100 4812641 http://www.medworm.com/index.php?rid=4705356&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470699%26dopt%3DAbstract Authors: Rusakov DA, Savtchenko LP, Zheng K, Henley JM Rapid communication in the brain relies on the release and diffusion of small transmitter molecules across the synaptic cleft. How these diffuse signals are transformed into cellular responses is determined by the scatter of target postsynaptic receptors, which in turn depends on receptor movement in cell membranes. Thus, by shaping information transfer in neural circuits, mechanisms that regulate molecular mobility affect nearly every aspect of brain function and dysfunction. Here we review two facets of molecular mobility that have traditionally been considered separately, namely extracellular and intra-membrane diffusion. By focusing on the interplay between these processes we illustrate the remarkable versatility of signal form... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4705356 Sun, 03 Apr 2011 23:00:00 +0100 4705356 http://www.medworm.com/index.php?rid=4705357&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21459463%26dopt%3DAbstract Authors: Feldt S, Bonifazi P, Cossart R Structure-function studies of neuronal networks have recently benefited from considerable progress in different areas of investigation. Advances in molecular genetics and imaging have allowed for the dissection of neuronal connectivity with unprecedented detail whereas in vivo recordings are providing much needed clues as to how sensory, motor and cognitive function is encoded in neuronal firing. However, bridging the gap between the cellular and behavioral levels will ultimately require an understanding of the functional organization of the underlying neuronal circuits. One way to unravel the complexity of neuronal networks is to understand how their connectivity emerges during brain maturation. In this review, we will describe how graph theory ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4705357 Fri, 01 Apr 2011 23:00:00 +0100 4705357 http://www.medworm.com/index.php?rid=4705358&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21459462%26dopt%3DAbstract Authors: Gutierrez H, Davies AM The nuclear factor-kappa B (NF-κB) family of transcription factors has recently emerged as a major regulator of the growth and elaboration of neural processes. NF-κB signaling has been implicated in controlling axon initiation, elongation, guidance and branching and in regulating dendrite arbor size and complexity during development and dendritic spine density in the adult. NF-κB is activated by a variety of extracellular signals, and either promotes or inhibits growth depending on the phosphorylation status of the p65 NF-κB subunit. These novel roles for NF-κB, together with recent evidence implicating NF-κB in the regulation of neurogenesis in the embryo and adult, have important implications for neural development and for learning and memory in ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4705358 Thu, 31 Mar 2011 23:00:00 +0100 4705358 http://www.medworm.com/index.php?rid=4646529&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21439656%26dopt%3DAbstract Authors: Baluch F, Itti L Attention exhibits characteristic neural signatures in brain regions that process sensory signals. An important area of future research is to understand the nature of top-down signals that facilitate attentional guidance towards behaviorally relevant locations and features. In this review, we discuss recent studies that have made progress towards understanding: (i) the brain structures and circuits involved in attentional allocation; (ii) top-down attention pathways, particularly as elucidated by microstimulation and lesion studies; (iii) top-down modulatory influences involving subcortical structures and reward systems; (iv) plausible substrates and embodiments of top-down signals; and (v) information processing and theoretical constraints that might be helpf... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4646529 Wed, 23 Mar 2011 00:00:00 +0100 4646529 http://www.medworm.com/index.php?rid=4646528&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21439657%26dopt%3DAbstract Authors: Kochubey O, Lou X, Schneggenburger R Transmitter release at synapses is driven by elevated intracellular Ca(2+) concentration ([Ca(2+)](i)) near the sites of vesicle fusion. [Ca(2+)](i) signals of profoundly different amplitude and kinetics drive the phasic release component during a presynaptic action potential, and asynchronous release at later times. Studies using direct control of [Ca(2+)](i) at a large glutamatergic terminal, the calyx of Held, have provided significant insight into how intracellular Ca(2+) regulates transmitter release over a wide concentration range. Synaptotagmin-2 (Syt2), the major isoform of the Syt1/2 Ca(2+) sensors at these synapses, triggers highly Ca(2+)-cooperative release above 1μM [Ca(2+)](i), but suppresses release at low [Ca(2+)](i). Thus, ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4646528 Wed, 23 Mar 2011 00:00:00 +0100 4646528 http://www.medworm.com/index.php?rid=4646530&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21420743%26dopt%3DAbstract Authors: Henley JM, Barker EA, Glebov OO Postsynaptic AMPA-type glutamate receptors (AMPARs) mediate most fast excitatory synaptic transmission and are crucial for many aspects of brain function, including learning, memory and cognition. The number, synaptic localization and subunit composition of synaptic AMPARs are tightly regulated by network activity and by the history of activity at individual synapses. Furthermore, aberrant AMPAR trafficking is implicated in neurodegenerative diseases. AMPARs therefore represent a prime target for drug development and the mechanisms that control their synaptic delivery, retention and removal are the subject of extensive research. Here, we review recent findings that have provided new insights into AMPAR trafficking and that might lead to the deve... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4646530 Fri, 18 Mar 2011 00:00:00 +0100 4646530 http://www.medworm.com/index.php?rid=4646531&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21419501%26dopt%3DAbstract Authors: Okun E, Griffioen KJ, Mattson MP Toll-like receptors (TLRs) are a family of innate immune system receptors that respond to pathogen-derived and tissue damage-related ligands. TLR signaling in immune cells, glia and neurons can play roles in the pathogenesis of stroke, Alzheimer's disease (AD) and multiple sclerosis (MS). Recent findings suggest that TLR signaling also influences multiple dynamic processes in the developing and adult central nervous system including neurogenesis, axonal growth and structural plasticity. In addition, TLRs are implicated in the regulation of behaviors including learning, memory and anxiety. This review describes recently discovered and unexpected roles for TLRs in neuroplasticity, and the implications of these findings for future basic and transl... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4646531 Wed, 16 Mar 2011 00:00:00 +0100 4646531 http://www.medworm.com/index.php?rid=4646532&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21397959%26dopt%3DAbstract Authors: Boyan GS, Reichert H The central complex of the insect brain is a remarkably miniaturized but highly complex multimodal information-processing network. Recent work on central complex development in Drosophila and grasshopper reveals that the cells comprising its complex circuitry are generated by a surprisingly small number of primary progenitors. Of these, four identified neural stem cells generate a large number of neurons through a novel mode of neurogenesis that involves self-renewing intermediate progenitor cells. Interestingly, a comparable mode of amplification of proliferation also operates in the developing mammalian cortex; this could be a general strategy for increasing brain size and complexity. Although this type of proliferation generates a large number of progen... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4646532 Fri, 11 Mar 2011 00:00:00 +0100 4646532 http://www.medworm.com/index.php?rid=4646533&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21397343%26dopt%3DAbstract Authors: Fu M, Zuo Y Synapses are the fundamental units of neuronal circuits. Synaptic plasticity can occur through changes in synaptic strength, as well as through the addition/removal of synapses. Two-photon microscopy in combination with fluorescence labeling offers a powerful tool to peek into the living brain and follow structural reorganization at individual synapses. Time-lapse imaging depicts a dynamic picture in which experience-dependent plasticity of synaptic structures varies between different cortical regions and layers, as well as between neuronal subtypes. Recent studies have demonstrated that the formation and elimination of synaptic structures happens rapidly in a subpopulation of cortical neurons during various sensorimotor learning experiences, and that stabilized sy... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4646533 Thu, 10 Mar 2011 00:00:00 +0100 4646533 http://www.medworm.com/index.php?rid=4582419&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21377221%26dopt%3DAbstract Authors: Sandi C Glucocorticoids can acutely affect memory processes, with both facilitating and impairing effects having been described. Recent work has revealed that glucocorticoids may affect learning and memory processes by interacting with glutamatergic mechanisms. In this opinion article I describe different glutamatergic pathways that glucocorticoids can affect to modulate memory processes. Furthermore, glucocorticoid-glutamatergic interactions during information processing are proposed as a potential model to explain many of the diverse actions of glucocorticoids on cognition. The model suggests that direct modulation of glutamatergic pathways by glucocorticoids could serve as an important mechanism for these hormones to directly alter cognitive functions. PMID: 21377221 [P... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4582419 Fri, 04 Mar 2011 00:00:00 +0100 4582419 http://www.medworm.com/index.php?rid=4582421&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21353710%26dopt%3DAbstract Authors: Tan KR, Rudolph U, Lüscher C Benzodiazepines are widely used clinically to treat anxiety and insomnia. They also induce muscle relaxation, control epileptic seizures, and can produce amnesia. Moreover, benzodiazepines are often abused after chronic clinical treatment and also for recreational purposes. Within weeks, tolerance to the pharmacological effects can develop as a sign of dependence. In vulnerable individuals with compulsive drug use, addiction will be diagnosed. Here we review recent observations from animal models regarding the cellular and molecular basis that might underlie the addictive properties of benzodiazepines. These data reveal how benzodiazepines, acting through specific GABA(A) receptor subtypes, activate midbrain dopamine neurons, and how this could hi... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4582421 Thu, 24 Feb 2011 00:00:00 +0100 4582421 http://www.medworm.com/index.php?rid=4582420&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21353711%26dopt%3DAbstract Authors: Zlokovic BV, Griffin JH Recent studies indicate that single-action-single-target agents are unlikely to cure CNS disorders sharing a pathogenic triad consisting of vascular damage, neuronal injury/neurodegeneration and neuroinflammation. Here we focus on a recent example of a multiple-action-multiple-target approach for CNS disorders based on newly discovered biological properties of activated protein C (APC), an endogenous plasma protease with antithrombotic, cytoprotective and anti-inflammatory activities in the CNS. We propose that APC-mediated signaling through the protease activated receptor-1 (PAR1) can favorably regulate multiple pathways within the neurovascular unit in non-neuronal cells and neurons during acute or chronic CNS insults, leading to stabilization of the ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4582420 Thu, 24 Feb 2011 00:00:00 +0100 4582420 http://www.medworm.com/index.php?rid=4528943&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21316770%26dopt%3DAbstract Authors: Gaillard A, Jaber M Cell replacement therapy has been proposed as a means to replace lost dopaminergic neurons in Parkinson's disease (PD). In most studies, the transplanted cells have been placed within the target site, the striatum, and not within the lesioned site, the substantia nigra, as the adult nigrostriatal pathway was thought to constitute a non-permissive environment for long distance axonal outgrowth of transplanted neuroblasts. Here, we discuss recent findings showing that intranigral transplanted dopaminergic neuroblasts can form axonal projections to the striatum, resulting in increased striatal dopamine levels and ameliorating behavioral deficits in animal models of PD. Such findings have raised new hopes and opened new avenues for cell replacement therapy in p... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4528943 Fri, 11 Feb 2011 00:00:00 +0100 4528943 http://www.medworm.com/index.php?rid=4528945&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21315458%26dopt%3DAbstract Authors: Proenca CC, Gao KP, Shmelkov SV, Rafii S, Lee FS Slitrks are a family of structurally related transmembrane proteins belonging to the leucine-rich repeat (LRR) superfamily. Six family members exist (Slitrk1-6) and all are highly expressed in the central nervous system (CNS). Slitrks have been implicated in mediating basic neuronal processes, ranging from neurite outgrowth and dendritic elaboration to neuronal survival. Recent studies in humans and genetic mouse models have led to the identification of Slitrks as candidate genes that might be involved in the development of neuropsychiatric conditions, such as obsessive compulsive spectrum disorders and schizophrenia. Although these system-level approaches have suggested that Slitrks play prominent roles in CNS development, key ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4528945 Wed, 09 Feb 2011 00:00:00 +0100 4528945 http://www.medworm.com/index.php?rid=4528944&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21315459%26dopt%3DAbstract Authors: Hatten ME, Roussel MF Medulloblastoma (MB) is the most common malignant pediatric brain tumor and is thought to arise from genetic anomalies in developmental pathways required for the normal maturation of the cerebellar cortex, notably developmental pathways for granule cell progenitor (GCP) neurogenesis. Over the past decade, a wide range of studies have identified genes and their regulators within signaling pathways, as well as noncoding RNAs, that have crucial roles in both normal cerebellar development and pathogenesis. These include the Notch, Wnt/β-catenin, bone morphogenic proteins (Bmp) and Sonic Hedgehog (Shh) pathways. In this review, we highlight the function of these pathways in the growth of the cerebellum and the formation of MB. A better understanding of the de... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4528944 Wed, 09 Feb 2011 00:00:00 +0100 4528944 http://www.medworm.com/index.php?rid=4411258&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21256604%26dopt%3DAbstract Authors: Contractor A, Mulle C, Swanson GT Two decades have passed since the first report of the cloning of a kainate-type glutamate receptor (KAR) subunit. The intervening years have seen a rapid growth in our understanding of the biophysical properties and function of KARs in the brain. This research has led to an appreciation that KARs play very distinct roles at synapses relative to other members of the glutamate-gated ion channel receptor family, despite structural and functional commonalities. The surprisingly diverse and complex nature of KAR signaling underlies their unique impact upon neuronal networks through their direct and indirect effects on synaptic transmission, and their prominent role in regulating cell excitability. This review pieces together highlights from the two... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4411258 Thu, 20 Jan 2011 00:00:00 +0100 4411258 http://www.medworm.com/index.php?rid=4411259&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21236501%26dopt%3DAbstract Authors: Allaman I, Bélanger M, Magistretti PJ In recent years, previously unsuspected roles of astrocytes have been revealed, largely owing to the development of new tools enabling their selective study in situ. These exciting findings add to the large body of evidence demonstrating that astrocytes play a central role in brain homeostasis, in particular via the numerous cooperative metabolic processes they establish with neurons, such as the supply of energy metabolites and neurotransmitter recycling functions. Furthermore, impairments in astrocytic function are increasingly being recognized as an important contributor to neuronal dysfunction and, in particular, neurodegenerative processes. In this review, we discuss recent evidence supporting important roles for astrocytes in neurop... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4411259 Wed, 12 Jan 2011 00:00:00 +0100 4411259 http://www.medworm.com/index.php?rid=4343572&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21196054%26dopt%3DAbstract Authors: Shamma SA, Elhilali M, Micheyl C Humans and other animals can attend to one of multiple sounds and follow it selectively over time. The neural underpinnings of this perceptual feat remain mysterious. Some studies have concluded that sounds are heard as separate streams when they activate well-separated populations of central auditory neurons, and that this process is largely pre-attentive. Here, we argue instead that stream formation depends primarily on temporal coherence between responses that encode various features of a sound source. Furthermore, we postulate that only when attention is directed towards a particular feature (e.g. pitch) do all other temporally coherent features of that source (e.g. timbre and location) become bound together as a stream that is segregated f... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4343572 Fri, 31 Dec 2010 00:00:00 +0100 4343572 http://www.medworm.com/index.php?rid=4343573&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21176975%26dopt%3DAbstract Authors: Green AM, Kalaska JF Brain-computer interfaces (BCIs) extract signals from neural activity to control remote devices ranging from computer cursors to limb-like robots. They show great potential to help patients with severe motor deficits perform everyday tasks without the constant assistance of caregivers. Understanding the neural mechanisms by which subjects use BCI systems could lead to improved designs and provide unique insights into normal motor control and skill acquisition. However, reports vary considerably about how much training is required to use a BCI system, the degree to which performance improves with practice and the underlying neural mechanisms. This review examines these diverse findings, their potential relationship with motor learning during overt arm movem... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4343573 Mon, 20 Dec 2010 00:00:00 +0100 4343573 http://www.medworm.com/index.php?rid=4343574&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21145601%26dopt%3DAbstract Authors: Capogna M, Pearce RA GABA(A) receptors in the CNS mediate both fast synaptic and tonic inhibition. Over the past decade a phasic current with features intermediate between fast synaptic and tonic inhibition, termed GABA(A,slow), has received increasing attention. This has coincided with an ever-growing appreciation for GABAergic cell type diversity. Compared with classical fast synaptic inhibition, GABA(A,slow) is slower by an order of magnitude. In this review, we summarize recent studies that have enhanced our understanding of GABA(A,slow). These include the discovery of specialized interneuron types from which this current originates, the factors that could underlie its characteristically slow kinetics, its contribution to specific aspects of integrative function and networ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4343574 Wed, 08 Dec 2010 00:00:00 +0100 4343574 http://www.medworm.com/index.php?rid=4343575&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21144600%26dopt%3DAbstract Authors: Aron L, Klein R No therapy exists to slow down or prevent Parkinson's disease (PD), a debilitating neurodegenerative disorder. Neurotrophic factors (NTFs) emerged as promising disease-modifying agents in PD and are currently under clinical development. We argue that efforts in three research areas must converge to harness the full therapeutic power of NTFs. First, the physiological roles of NTFs in aging dopaminergic neurons must be comprehensively understood. Second, the mechanisms underlying the neuroprotective, neurorestorative and stimulatory effects of NTFs on diseased neurons need to be defined. Third, improved brain delivery of NTFs and new ways to stimulate NTF signaling are required to achieve clinical benefits. In this review, we discuss progress in these areas and h... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4343575 Mon, 06 Dec 2010 00:00:00 +0100 4343575 http://www.medworm.com/index.php?rid=4251875&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21129791%26dopt%3DAbstract Authors: Fame RM, Macdonald JL, Macklis JD Callosal projection neurons (CPN) are a diverse population of neocortical projection neurons that connect the two hemispheres of the cerebral cortex via the corpus callosum. They play key roles in high-level associative connectivity, and have been implicated in cognitive syndromes of high-level associative dysfunction, such as autism spectrum disorders. CPN evolved relatively recently compared to other cortical neuron populations, and have undergone disproportionately large expansion from mouse to human. While much is known about the anatomical trajectory of developing CPN axons, and progress has been made in identifying cellular and molecular controls over midline crossing, only recently have molecular-genetic controls been identified that sp... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4251875 Wed, 01 Dec 2010 00:00:00 +0100 4251875 http://www.medworm.com/index.php?rid=4169021&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21056479%26dopt%3DAbstract Authors: Davidson S, Giesler GJ Multiple neural pathways and molecular mechanisms responsible for producing the sensation of itch have recently been identified, including histamine-independent pathways. Physiological, molecular, behavioral and brain imaging studies are converging on a description of these pathways and their close association with pain processing. Some conflicting results have arisen and the precise relationship between itch and pain remains controversial. A better understanding of the generation of itch and of the intrinsic mechanisms that inhibit itch after scratching should facilitate the search for new methods to alleviate clinical pruritus (itch). In this review we describe the current understanding of the production and inhibition of itch. A model of itch processi... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4169021 Tue, 16 Nov 2010 06:35:53 +0100 4169021 http://www.medworm.com/index.php?rid=4169020&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21067824%26dopt%3DAbstract Authors: Holtzheimer PE, Mayberg HS The current definition of major depressive disorder (MDD) emerged from efforts to create reliable diagnostic criteria for clinical and research use. However, despite decades of research, the neurobiology of MDD is largely unknown, and treatments are no more effective today than they were 50-70 years ago. Here, we propose that the current conception of depression is misguiding basic and clinical research. Redefinition is necessary and could include a focus on a more narrowly defined set of core symptoms. However, we conclude that depression is better defined as the tendency to enter into, and inability to disengage from, a negative mood state rather than the mood state per se. We also discuss the implications of this revised definition for future clin... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4169020 Mon, 08 Nov 2010 00:00:00 +0100 4169020 http://www.medworm.com/index.php?rid=4169019&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21067825%26dopt%3DAbstract Authors: O'Donnell C, Nolan MF Neuron types are classically defined by anatomical and physiological properties that determine how synaptic inputs are integrated. Here, we provide an overview of the evidence that, among neurons of a single type, integration of synaptic responses is further tuned according to the particular function that individual neurons carry out. Recent data suggest that tuning of synaptic responses is not restricted to sensory pathways, but extends to cognitive and motor circuits. We propose that tuning of synaptic integration results from general cellular mechanisms for optimization of information processing that are distinct from, but complementary to, homeostasis and memory storage. These cellular tuning mechanisms might be crucial for distributed computations un... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4169019 Mon, 08 Nov 2010 00:00:00 +0100 4169019 http://www.medworm.com/index.php?rid=4139879&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21035199%26dopt%3DAbstract Authors: Andrews ZB Ghrelin is a peptide hormone produced and secreted in the stomach. Numerous studies over the past decade demonstrate its importance in food intake, body-weight regulation and glucose homeostasis. These effects are driven largely by the high expression of the ghrelin receptor (GHSR1a) in the hypothalamus. However, GHSR1a is also expressed in numerous extra-hypothalamic neuronal populations, suggesting that ghrelin has physiological functions besides those involved in metabolic functions. In this review, I focus on increasing evidence that ghrelin has important roles in extra-hypothalamic functions, including learning and memory, reward and motivation, anxiety and depression, and neuroprotection. Furthermore, I discuss how the recently demonstrated role of ghrelin in ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4139879 Wed, 27 Oct 2010 00:00:00 +0100 4139879 http://www.medworm.com/index.php?rid=4125323&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21030095%26dopt%3DAbstract Authors: Kilduff TS, Cauli B, Gerashchenko D Although slow wave activity in the EEG has been linked to homeostatic sleep regulation, the neurobiological substrate of sleep homeostasis is not well understood. Whereas cortical neurons typically exhibit reduced discharge rates during slow wave sleep (SWS), a subpopulation of GABAergic interneurons, which express the enzyme neuronal nitric oxide synthase (nNOS), has recently been found to be activated during SWS. The extent of activation of these nNOS neurons is proportional to homeostatic sleep 'drive'. These cells are an exception among cortical interneurons in that they are projection neurons. We propose that cortical nNOS neurons are positioned to influence neuronal activity across widespread brain areas. They could thus provide a long... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4125323 Tue, 26 Oct 2010 00:00:00 +0100 4125323 http://www.medworm.com/index.php?rid=4125324&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20980064%26dopt%3DAbstract Authors: Lazarini F, Lledo PM In mammals, new neurons are recruited into restricted brain areas throughout life. Adult-born neurons produced in the subventricular zone of the lateral ventricle migrate rostrally towards the olfactory bulb. Although thousands of neurons reach this central structure every day, the functional impact of their integration into mature circuits remains a matter of debate. Recent investigations have revealed no striking sensory deficits per se when adult bulbar neurogenesis is challenged. However, some cognitive functions, such as perceptual learning and olfactory memory, are clearly impaired. In this review we highlight the role of network activity in shaping ongoing neurogenesis and, in turn, how the integration of adult-born neurons refines pre-existing netw... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4125324 Mon, 25 Oct 2010 00:00:00 +0100 4125324 http://www.medworm.com/index.php?rid=4088847&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20961626%26dopt%3DAbstract Authors: Venda LL, Cragg SJ, Buchman VL, Wade-Martins R α-Synuclein is central to the Lewy body neuropathology of Parkinson's disease (PD), a devastating neurodegenerative disorder characterized by numerous motor and non-motor manifestations. The cardinal motor symptoms are linked to death of dopaminergic neurons in the nigrostriatal pathway. Here we ask why these neurons are preferentially susceptible to neurodegeneration in PD and how α-synuclein is involved. To address these questions we bring together recent findings from genome-wide association studies, which reveal the involvement of α-synuclein gene variants in sporadic PD, with recent studies highlighting important roles for α-synuclein in synaptic transmission and dopaminergic neuron physiology. These latest advances add t... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4088847 Sun, 17 Oct 2010 23:00:00 +0100 4088847 http://www.medworm.com/index.php?rid=4088846&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20961627%26dopt%3DAbstract Authors: Lazarov O, Mattson MP, Peterson DA, Pimplikar SW, van Praag H In this review, we consider the evidence that a reduction in neurogenesis underlies aging-related cognitive deficits and impairments in disorders such as Alzheimer's disease (AD). The molecular and cellular alterations associated with impaired neurogenesis in the aging brain are discussed. Dysfunction of presenilin-1, misprocessing of amyloid precursor protein and toxic effects of hyperphosphorylated tau and β-amyloid probably contribute to impaired neurogenesis in AD. Because factors such as exercise, environmental enrichment and dietary energy restriction enhance neurogenesis, and protect against age-related cognitive decline and AD, knowledge of the underlying neurogenic signaling pathways could lead to novel th... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4088846 Sun, 17 Oct 2010 23:00:00 +0100 4088846 http://www.medworm.com/index.php?rid=4077908&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20947179%26dopt%3DAbstract Authors: Banerjee R, Beal MF, Thomas B Autophagy is a highly conserved intracellular pathway involved in the elimination of proteins and organelles by lysosomes. Known originally as an adaptive response to nutrient deprivation in mitotic cells, autophagy is now recognized as an arbiter of neuronal survival and death decisions in neurodegenerative diseases. Studies using postmortem human tissue, genetic and toxin-induced animal and cellular models indicate that many of the etiological factors associated with neurodegenerative disorders can perturb the autophagy process. Emerging data support the view that dysregulation of autophagy might play a critical role in the pathogenesis of neurodegenerative disorders. In this review, we highlight the pathophysiological roles of autophagy and its... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4077908 Mon, 11 Oct 2010 23:00:00 +0100 4077908 http://www.medworm.com/index.php?rid=4009721&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20864190%26dopt%3DAbstract Authors: Wilson CR, Gaffan D, Browning PG, Baxter MG Anatomical and functional studies of the prefrontal cortex (PFC) have identified multiple PFC subregions. We argue that the PFC is involved in cognitive functions exceeding the sum of specific functions attributed to its subregions. These can be revealed either by lesions of the whole PFC, or more specifically by selective disconnection of the PFC from certain types of information (for example, visual) allowing the investigation of PFC function in toto. Recent studies in macaque monkeys using the latter approach lead to a second conclusion: that the PFC, as a whole, could be fundamentally specialized for representing events that are extended in time. The representation of temporally complex events might underlie PFC involvement in ge... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4009721 Tue, 21 Sep 2010 23:00:00 +0100 4009721 http://www.medworm.com/index.php?rid=4009719&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20869126%26dopt%3DAbstract Authors: Jörntell H, Bengtsson F, Schonewille M, De Zeeuw CI In recent years there has been an increased interest in the function of inhibitory interneurons. In the cerebellum this interest has been paired with successes in obtaining recordings from these neurons in vivo and genetic manipulations to probe their function during behavioral tasks such as motor learning. This review focuses on a synthesis of recent findings on the computational properties that these neurons confer to the cerebellar circuitry and on their recently discovered capacity for plasticity and learning in vivo. Since the circuitry of the cerebellar cortex is relatively well-defined, the specificity with which the potential roles of these interneurons can be described will help to guide new avenues of research on... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4009719 Tue, 21 Sep 2010 23:00:00 +0100 4009719 http://www.medworm.com/index.php?rid=4009720&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20864191%26dopt%3DAbstract Authors: Ben-Ari Y, Spitzer NC Nervous system development proceeds by sequential gene expression mediated by cascades of transcription factors in parallel with sequences of patterned network activity driven by receptors and ion channels. These sequences are cell type- and developmental stage-dependent and modulated by paracrine actions of substances released by neurons and glia. How and to what extent these sequences interact to enable neuronal network development is not understood. Recent evidence demonstrates that CNS development requires intermediate stages of differentiation providing functional feedback that influences gene expression. We suggest that embryonic neuronal functions constitute a series of phenotypic checkpoint signatures; neurons failing to express these functions ar... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=4009720 Mon, 20 Sep 2010 23:00:00 +0100 4009720 http://www.medworm.com/index.php?rid=3988368&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20850189%26dopt%3DAbstract Authors: Milnerwood AJ, Raymond LA Investigations of synaptic transmission and plasticity in mouse models of Huntington's disease (HD) demonstrate neuronal dysfunction long before the onset of classical disease indicators. Similarly, recent human studies reveal synaptic dysfunction decades before predicted clinical diagnosis in HD gene carriers. These studies guide premanifest tracking of disease and the development of treatment assessment tools. New discoveries of mechanisms underlying early neuronal dysfunction, including elevated pathogenic extrasynaptic NMDA receptor signaling, reduced synaptic connectivity and loss of brain-derived neurotrophic factor (BDNF) support have led to pharmacological interventions that can reverse or delay phenotype onset and disease progression in HD mi... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3988368 Tue, 14 Sep 2010 23:00:00 +0100 3988368 http://www.medworm.com/index.php?rid=3988369&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20843563%26dopt%3DAbstract Authors: Sen N, Snyder SH Covalent modifications of intracellular proteins, such as phosphorylation, are generally thought to occur as secondary or tertiary responses to neurotransmitters, following the intermediation of membrane receptors and second messengers such as cyclic AMP. By contrast, the gasotransmitter nitric oxide directly S-nitrosylates cysteine residues in diverse intracellular proteins. Recently, hydrogen sulfide has been acknowledged as a gasotransmitter, which analogously sulfhydrates cysteine residues in proteins. Cysteine residues are also modified by palmitoylation in response to neurotransmitter signaling, possibly in reciprocity with S-nitrosylation. Neurotransmission also elicits sumoylation and acetylation of lysine residues within diverse proteins. This review ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3988369 Mon, 13 Sep 2010 23:00:00 +0100 3988369 http://www.medworm.com/index.php?rid=3973756&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20832872%26dopt%3DAbstract Authors: Leuner B, Glasper ER, Gould E As any new parent knows, having a baby provides opportunities for enrichment, learning and stress - experiences known to change the adult brain. Yet surprisingly little is known about the effects of maternal experience, and even less about the effects of paternal experience, on neural circuitry not directly involved in parenting. Here we discuss how caregiving and the accompanying experiential and hormonal changes influence the hippocampus and prefrontal cortex, brain regions involved in cognition and mood regulation. A better understanding of how parenting impacts the brain is likely to help in devising strategies for treating parental depression, a condition that can have serious cognitive and mental health consequences for children. PMID: 2... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3973756 Wed, 08 Sep 2010 23:00:00 +0100 3973756 http://www.medworm.com/index.php?rid=3973755&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20832873%26dopt%3DAbstract Authors: Dityatev A, Seidenbecher CI, Schachner M The extracellular matrix (ECM) of the central nervous system is well recognized as a migration and diffusion barrier that allows for the trapping and presentation of growth factors to their receptors at the cell surface. Recent data highlight the importance of ECM molecules as synaptic and perisynaptic scaffolds that direct the clustering of neurotransmitter receptors in the postsynaptic compartment and that present barriers to reduce the lateral diffusion of membrane proteins away from synapses. The ECM also contributes to the migration and differentiation of stem cells in the neurogenic niche and organizes the polarized localization of ion channels and transporters at contacts between astrocytic processes and blood vessels. Thus, the ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3973755 Wed, 08 Sep 2010 23:00:00 +0100 3973755 http://www.medworm.com/index.php?rid=3973757&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20832128%26dopt%3DAbstract Authors: Krack P, Hariz MI, Baunez C, Guridi J, Obeso JA Functional stereotaxy was introduced in the late 1940s to reduce the morbidity of lobotomy in psychiatric disease by using more focal lesions. The advent of neuroleptics led to a drastic decline in psychosurgery for several decades. Functional stereotactic neurosurgery has recently been revitalized, starting with treatment of Parkinson's disease, in which deep brain stimulation (DBS) facilitates reversible focal neuromodulation of altered basal ganglia circuits. DBS is now being extended to treatment of neuropsychiatric conditions such as Gilles de la Tourette syndrome, obsessive-compulsive disorder, depression and addiction. In this review, we discuss the concept that dysfunction of motor, limbic and associative cortico-basal ga... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3973757 Tue, 07 Sep 2010 23:00:00 +0100 3973757 http://www.medworm.com/index.php?rid=3865620&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20701984%26dopt%3DAbstract Authors: Waddell S A goal of memory research is to understand how changing the weight of specific synapses in neural circuits in the brain leads to an appropriate learned behavioral response. Finding the relevant synapses should allow investigators to probe the underlying physiological and molecular operations that encode memories and permit their retrieval. In this review I discuss recent work in Drosophila that implicates specific subsets of dopaminergic (DA) neurons in aversive reinforcement and appetitive motivation. The zonal architecture of these DA neurons is likely to reveal the functional organization of aversive and appetitive memory in the mushroom bodies. Combinations of fly DA neurons might code negative and positive value, consistent with a motivational systems role as pr... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3865620 Sun, 08 Aug 2010 23:00:00 +0100 3865620 http://www.medworm.com/index.php?rid=3795550&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655604%26dopt%3DAbstract Authors: Wolf ME Activation of medium spiny neurons (MSNs) of the nucleus accumbens is critical for goal-directed behaviors including cocaine seeking. Studies in cocaine-experienced rodents have revealed three major categories of neuroadaptations that influence the ability of glutamate inputs to activate MSNs: changes in synaptic AMPA receptor levels, changes in extracellular non-synaptic glutamate levels and changes in MSN intrinsic membrane excitability. Most studies have focused on one of these adaptations. This review will consider the possibility that they are causally related and speculate about how time-dependent changes in their interactions may regulate MSN output during early and late withdrawal from repeated cocaine exposure. PMID: 20655604 [PubMed - as supplied by publi... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3795550 Wed, 21 Jul 2010 23:00:00 +0100 3795550 http://www.medworm.com/index.php?rid=3767239&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20633936%26dopt%3DAbstract Authors: Gershon MD Enteric nervous system (ENS) development is relevant to Hirschsprung's disease (HSCR; congenital aganglionosis of the terminal bowel), which is still imperfectly treated. Mutations in genes encoding the RET receptor tyrosine kinase and endothelin receptor type B (EDNRB) are involved in HSCR pathogenesis; however, also important in ENS development are molecules that mediate events that are more restricted than those of RET and EDNRB, act later in development and which might not be HSCR-associated. Examples are molecules that function in the guidance of enteric neural crest-derived cells (ENCDCs) and vagal axons, and in regulating the terminal differentiation of enteric neurons from ENCDCs. It is probable that highly prevalent disorders of gastrointestinal sensation a... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3767239 Mon, 12 Jul 2010 23:00:00 +0100 3767239 http://www.medworm.com/index.php?rid=3742749&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20598379%26dopt%3DAbstract Authors: Frotscher M Reelin controls the migration of neurons and layer formation during brain development. However, recent studies have shown that disrupting Reelin function in the adult hippocampus induces repositioning of fully differentiated neurons, suggesting a stabilizing effect of Reelin on mature neuronal circuitry. Indeed, Reelin was recently found to stabilize the actin cytoskeleton by inducing cofilin phosphorylation. When unphosphorylated, cofilin acts as an actin-depolymerizing protein that promotes the disassembly of F-actin. Here, a novel hypothesis is proposed whereby decreased Reelin expression in the mature brain causes destabilization of neurons and their processes, leading to aberrant plasticity and aberrant wiring of brain circuitry. This has implications for brai... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3742749 Tue, 29 Jun 2010 23:00:00 +0100 3742749 http://www.medworm.com/index.php?rid=3702120&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20573407%26dopt%3DAbstract Authors: O'Reilly RC How is the prefrontal cortex (PFC) organized such that it is capable of making people more flexible and in control of their behavior? Is there any systematic organization across the many diverse areas that comprise the PFC, or is it uniquely adaptive such that no fixed representational structure can develop? Going against the current tide, this paper argues that there is indeed a systematic organization across PFC areas, with an important functional distinction between ventral and dorsal regions characterized as processing What versus How information, respectively. This distinction has implications for the rostro-caudal and medial-lateral axes of organization as well. The resulting large-scale functional map of PFC could prove useful in integrating diverse data, an... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3702120 Sun, 20 Jun 2010 23:00:00 +0100 3702120 http://www.medworm.com/index.php?rid=3692007&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20561690%26dopt%3DAbstract Authors: Daubert EA, Condron BG Serotonin is an important neuromodulator associated with a wide range of physiological effects in the central nervous system. The exact mechanisms whereby serotonin influences brain development are not well understood, although studies in invertebrate and vertebrate model organisms are beginning to unravel a regulatory role for serotonin in neuronal morphology and circuit formation. Recent data suggest a developmental window during which altered serotonin levels permanently influence neuronal circuitry, however, the temporal constraints and molecular mechanisms responsible are still under investigation. Growing evidence suggests that alterations in early serotonin signaling contribute to a number of neurodevelopmental and neuropsychiatric disorders. Thus... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3692007 Wed, 16 Jun 2010 23:00:00 +0100 3692007 http://www.medworm.com/index.php?rid=3663092&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20541813%26dopt%3DAbstract Authors: Janke C, Kneussel M In the past decades, a range of post-translational modifications has been discovered on tubulins, the major constituents of microtubules. Pioneering studies have described the occurrence and dynamics of these modifications and provided first insights into their potential functions in regulating the microtubule cytoskeleton. By contrast, several tubulin-modifying enzymes were only discovered in the last few years, and studies on molecular mechanisms and cellular functions of tubulin modifications are just beginning to emerge. This review highlights the roles of tubulin modifications in neurons. Recent studies are also discussed in relation to how the combinatorial use of tubulin modifications could generate a dynamic microtubule code, and how such a code mig... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3663092 Wed, 09 Jun 2010 23:00:00 +0100 3663092 http://www.medworm.com/index.php?rid=3663091&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20541814%26dopt%3DAbstract Authors: Scholpp S, Lumsden A The thalamus is a central brain region that plays a crucial role in distributing incoming sensory information to appropriate regions of the cortex. The thalamus develops in the posterior part of the embryonic forebrain, where early cell fate decisions are controlled by a local signaling center - the mid-diencephalic organizer - which forms at the boundary between prospective prethalamus and thalamus. In this review we discuss recent observations of early thalamic development in zebrafish, chick, and mouse embryos, that reveal a conserved set of interactions between homeodomain transcription factors. These interactions position the organizer along the neuraxis. The most prominent of the organizer's signals, Sonic hedgehog, is necessary for conferring region... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3663091 Wed, 09 Jun 2010 23:00:00 +0100 3663091 http://www.medworm.com/index.php?rid=3663090&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20542579%26dopt%3DAbstract Authors: Zahs KR, Ashe KH Scores of compounds ameliorate cognitive deficits or neuropathology in transgenic mouse models of Alzheimer's disease (AD), yet these triumphs in mice have not translated into successful therapies for people. Why have studies in mice failed to predict results of human trials? We argue that most transgenic mouse 'models of AD' actually simulate the asymptomatic phase of the disease, and the results of interventional studies in these mice should be considered in the context of disease prevention. In addition, recent advances in imaging technology and biomarker discovery should aid in comparisons of mouse and human neurological status and, importantly, might allow us to predict better the response of people to drugs tested in mice. PMID: 20542579 [PubMed - as... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3663090 Wed, 02 Jun 2010 23:00:00 +0100 3663090 http://www.medworm.com/index.php?rid=3600193&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20493563%26dopt%3DAbstract Authors: Carleton A, Accolla R, Simon SA To understand gustatory physiology and associated dysfunctions it is important to know how oral taste stimuli are encoded both in the periphery and in taste-related brain centres. The identification of distinct taste receptors, together with electrophysiological recordings and behavioral assessments in response to taste stimuli, suggest that information about distinct taste modalities (e.g. sweet versus bitter) are transmitted from the periphery to the brain via segregated pathways. By contrast, gustatory neurons throughout the brain are more broadly tuned, indicating that ensembles of neurons encode taste qualities. Recent evidence reviewed here suggests that the coding of gustatory stimuli is not immutable, but is dependant on a variety of fac... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3600193 Tue, 18 May 2010 23:00:00 +0100 3600193 http://www.medworm.com/index.php?rid=3600192&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20493564%26dopt%3DAbstract Authors: Goedert M, Clavaguera F, Tolnay M The most common neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, are characterized by the misfolding of a small number of proteins that assemble into ordered aggregates in affected brain cells. For many years, the events leading to aggregate formation were believed to be entirely cell-autonomous, with protein misfolding occurring independently in many cells. Recent research has now shown that cell non-autonomous mechanisms are also important for the pathogenesis of neurodegenerative diseases with intracellular filamentous inclusions. The intercellular transfer of inclusions made of tau, alpha-synuclein, huntingtin and superoxide dismutase 1 has been demonstrated, revealing the existence of mechanisms reminisce... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3600192 Tue, 18 May 2010 23:00:00 +0100 3600192 http://www.medworm.com/index.php?rid=3582380&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20471112%26dopt%3DAbstract Authors: Singer T, McConnell MJ, Marchetto MC, Coufal NG, Gage FH LINE-1 (L1) elements are retrotransposons that insert extra copies of themselves throughout the genome using a 'copy and paste' mechanism. L1s comprise nearly approximately 20% of the human genome and are able to influence chromosome integrity and gene expression upon reinsertion. Recent studies show that L1 elements are active and 'jumping' during neuronal differentiation. New somatic L1 insertions could generate 'genomic plasticity' in neurons by causing variation in genomic DNA sequences and by altering the transcriptome of individual cells. Thus, L1-induced variation could affect neuronal plasticity and behavior. We discuss potential consequences of L1-induced neuronal diversity and propose that a mechanism for gener... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3582380 Tue, 11 May 2010 23:00:00 +0100 3582380 http://www.medworm.com/index.php?rid=3531479&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20434225%26dopt%3DAbstract Authors: Perlson E, Maday S, Fu MM, Moughamian AJ, Holzbaur EL Active transport along the axon is crucial to the neuron. Motor-driven transport supplies the distal synapse with newly synthesized proteins and lipids, and clears damaged or misfolded proteins. Microtubule motors also drive long-distance signaling along the axon via signaling endosomes. Although positive signaling initiated by neurotrophic factors has been well-studied, recent research has focused on stress-signaling along the axon. Here, the connections between axonal transport alterations and neurodegeneration are discussed, including evidence for defective transport of vesicles, mitochondria, degradative organelles, and signaling endosomes in models of amyotrophic lateral sclerosis, Huntington's, Parkinson's and Alzheim... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3531479 Tue, 27 Apr 2010 23:00:00 +0100 3531479 http://www.medworm.com/index.php?rid=3483548&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20398949%26dopt%3DAbstract This article highlights mechanisms by which the mRNAs with abnormally expanded repeats can confer toxicity leading to neuronal dysfunction and loss. Greater understanding of these mechanisms will provide the foundation for therapeutic advances for this set of human disorders. PMID: 20398949 [PubMed - as supplied by publisher] (Source: Trends in Neurosciences) Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3483548 Tue, 13 Apr 2010 23:00:00 +0100 3483548 http://www.medworm.com/index.php?rid=3450196&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20371122%26dopt%3DAbstract Authors: Borst JG The release probability, the average probability that an active zone of a presynaptic terminal releases one or more vesicles following an action potential, is tightly regulated. Measurements in cultured neurons or in slices indicate that this probability can vary greatly between synapses, but on average it is estimated to be as high as 0.5. In vivo, however, the size of synaptic potentials is relatively independent of recent history, suggesting that release probability is much lower. Possible causes for this discrepancy include maturational differences, a higher spontaneous activity, a lower extracellular calcium concentration and more prominent tonic inhibition by ambient neurotransmitters during in vivo recordings. Existing evidence thus suggests that under physiolo... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3450196 Fri, 02 Apr 2010 23:00:00 +0100 3450196 http://www.medworm.com/index.php?rid=3450197&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20363038%26dopt%3DAbstract Authors: Shah MM, Hammond RS, Hoffman DA Dendritic ion channels are essential for the regulation of intrinsic excitability as well as modulating the shape and integration of synaptic signals. Changes in dendritic channel function have been associated with many forms of synaptic plasticity. Recent evidence suggests that dendritic ion channel modulation and trafficking could contribute to plasticity-induced alterations in neuronal function. In this review we discuss our current knowledge of dendritic ion channel modulation and trafficking and their relationship to cellular and synaptic plasticity. We also consider the implications for neuronal function. We argue that to gain an insight into neuronal information processing it is essential to understand the regulation of dendritic ion chan... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3450197 Wed, 31 Mar 2010 23:00:00 +0100 3450197 http://www.medworm.com/index.php?rid=3435139&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20356635%26dopt%3DAbstract Authors: Mizuno K, Giese KP Sex differences exist in brain function and behavior. However, the underlying molecular mechanisms are only beginning to emerge. Recent studies in rodents have revealed molecular mechanisms underlying sex differences in memory formation. It is becoming clear that sex differences are not simply reflective of differences in sex hormones, but also reflect distinctions in synaptic signaling mechanisms including the role of synaptic kinases. Furthermore, there are sex differences in the activation of transcription factors and gene transcription during memory formation. This review discusses emerging evidence in the field and how these findings are providing a first step towards a molecular understanding of how sex differences impact on memory formation both in he... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3435139 Sun, 28 Mar 2010 23:00:00 +0100 3435139 http://www.medworm.com/index.php?rid=3391304&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20303187%26dopt%3DAbstract Authors: Wang DO, Martin KC, Zukin RS mRNA localization and regulated translation provide a means of spatially restricting gene expression within each of the thousands of subcellular compartments made by a neuron, thereby vastly increasing the computational capacity of the brain. Recent studies reveal that local translation is regulated by stimuli that trigger neurite outgrowth and/or collapse, axon guidance, synapse formation, pruning, activity-dependent synaptic plasticity, and injury-induced axonal regeneration. Impairments in the local regulation of translation result in aberrant signaling, physiology and morphology of neurons, and are linked to neurological disorders. This review highlights current advances in understanding how mRNA translation is repressed during transport and ho... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3391304 Thu, 18 Mar 2010 00:00:00 +0100 3391304 http://www.medworm.com/index.php?rid=3374531&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20227117%26dopt%3DAbstract Authors: Lemmens R, Moore MJ, Al-Chalabi A, Brown RH, Robberecht W The pathogenic mechanisms of degenerative diseases of the nervous system are not well understood. Recent evidence suggests that proteins with a role in RNA synthesis, processing, function and degradation play a role in the mechanism of degenerative disorders affecting the motor neuron. However, most of these proteins also affect cellular processes other than RNA processing. Furthermore, many of the familial diseases are inherited dominantly, suggesting a gain-of-function as their pathogenic mechanism. This newly gained function could be unrelated to their normal role in the cell. Therefore, here we review some of the recent data linking RNA metabolism and motor neuron disorders, but also critically assess their relevanc... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3374531 Thu, 11 Mar 2010 00:00:00 +0100 3374531 http://www.medworm.com/index.php?rid=3374533&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20226542%26dopt%3DAbstract Authors: Schorge S, van de Leemput J, Singleton A, Houlden H, Hardy J A persistent mystery about the ataxias has been why mutations in genes - many of which are expressed widely in the brain - primarily cause ataxia, and not, for example, epilepsy or dementia. Why should a polyglutamine stretch in the TATA-binding protein (that is important in all cells) particularly disrupt cerebellar coordination? We propose that advances in the genetics of cerebellar ataxias suggest a rational hypothesis for how so many different genes lead to predominantly cerebellar defects. We argue that the unifying feature of many genes involved in cerebellar ataxias is their impact on the signaling protein ITPR1 (inositiol 1,4,5-triphosphate receptor type 1), that underlies coincidence detection in Purkinje ce... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3374533 Wed, 10 Mar 2010 00:00:00 +0100 3374533 http://www.medworm.com/index.php?rid=3374532&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20226543%26dopt%3DAbstract Authors: Northoff G, Qin P, Nakao T Studies in animals and humans have demonstrated intrinsic activity in the brain during the resting state. The concept of the default-mode network (DMN) - a set of brain regions in which resting-state activity (RSA) activity is reduced in response to external stimuli - recently raised much controversy concerning the psychological correlates of RSA. However, it remains unclear how RSA interacts with stimulus-induced activity. Here we review studies in humans and animals that address how RSA interacts with stimulus-induced activity; we also discuss, conversely, how stimulus-induced activity can modulate RSA. Psychologically, the rest-stimulus interaction is relevant to predicting subsequent behavioral and mental states. We conclude that a better underst... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3374532 Wed, 10 Mar 2010 00:00:00 +0100 3374532 http://www.medworm.com/index.php?rid=3362824&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20223527%26dopt%3DAbstract Authors: Benito E, Barco A The activation of cAMP-response element binding protein (CREB)-dependent gene expression seems a crucial step in the molecular cascade that mediates the formation of long-lasting memories. This view is based both on correlative evidence and on functional assays that demonstrate, through loss- and gain-of-function experiments, the impact of CREB manipulation on memory performance. Mechanistically, CREB's role in memory is thought to be a consequence of its participation in long-term forms of synaptic plasticity. Recent studies demonstrate that CREB, in addition to synaptic plasticity, also modulates the intrinsic excitability of the neuron. This discovery reveals new intriguing connections between intrinsic and synaptic plasticity and is likely to have a signi... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3362824 Tue, 09 Mar 2010 00:00:00 +0100 3362824 http://www.medworm.com/index.php?rid=3362825&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20219255%26dopt%3DAbstract Authors: Kato AS, Gill MB, Yu H, Nisenbaum ES, Bredt DS Transmembrane AMPA receptor regulatory proteins (TARPs) are the first identified auxiliary subunits for a neurotransmitter-gated ion channel. Although initial studies found that stargazin, the prototypical TARP, principally chaperones AMPA receptors, subsequent research demonstrated that it also regulates AMPA receptor kinetics and synaptic waveforms. Recent studies have identified a diverse collection of TARP isoforms - types Ia, Ib II - that distinctly regulate AMPA receptor trafficking, gating and neuropharmacology. These TARP isoforms are heterogeneously expressed in specific neuronal populations and can differentially sculpt synaptic transmission and plasticity. Whole-genome analyses also link multiple TARP loci to childhood ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3362825 Mon, 08 Mar 2010 00:00:00 +0100 3362825 http://www.medworm.com/index.php?rid=3355087&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20207024%26dopt%3DAbstract Authors: Russo SJ, Dietz DM, Dumitriu D, Morrison JH, Malenka RC, Nestler EJ Addictive drugs cause persistent restructuring of several neuronal cell types in the limbic regions of brain thought to be responsible for long-term behavioral plasticity driving addiction. Although these structural changes are well documented in nucleus accumbens medium spiny neurons, little is known regarding the underlying molecular mechanisms. Additionally, it remains unclear whether structural plasticity and its synaptic concomitants drive addictive behaviors or whether they reflect homeostatic compensations to the drug not related to addiction per se. Here, we discuss recent paradoxical data, which either support or oppose the hypothesis that drug-induced changes in dendritic spines drive addictive behav... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3355087 Thu, 04 Mar 2010 00:00:00 +0100 3355087 http://www.medworm.com/index.php?rid=3355086&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20207025%26dopt%3DAbstract Authors: O'Neill J, Pleydell-Bouverie B, Dupret D, Csicsvari J Episodic and spatial memories each involve the encoding of complex associations in hippocampal neuronal circuits. Such memory traces could be stabilised from short- to long-term forms by consolidation processes involving the 'reactivation' of the original network firing patterns during sleep and rest. Waking experience can be replayed in many different brain areas, but an important role for the hippocampus lies in the organisation of the 'reactivation' process. Emerging evidence suggests that sharp wave/ripple (SWR) events in the hippocampus could coordinate the reactivation of memory traces and direct their reinstatement in cortical circuits. Although the mechanisms remain uncertain, there is a growing consensus that such ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3355086 Thu, 04 Mar 2010 00:00:00 +0100 3355086 http://www.medworm.com/index.php?rid=3285826&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20153532%26dopt%3DAbstract Authors: Siffrin V, Vogt J, Radbruch H, Nitsch R, Zipp F Recently it has become clear that the neuronal compartment plays a more important role than previously thought in the pathology of multiple sclerosis. Apart from demyelination, neuronal pathology is apparently largely responsible for the brain atrophy that can be observed early on and throughout the course of the disease. The loss of axons and their neurons in the course of chronic neuroinflammation is a major factor determining long-term disability in patients. The actual steps leading from immune attack against the myelin sheath to neuronal damage are not yet fully clear. Here we review key findings about direct axonal damage processes, demyelination-related neuronal pathology and cell-body pathology, the major pathologic corre... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3285826 Thu, 11 Feb 2010 00:00:00 +0100 3285826 http://www.medworm.com/index.php?rid=3285828&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20153060%26dopt%3DAbstract Authors: Ruthazer ES, Aizenman CD To successfully interact with their environments, developing organisms need to correctly process sensory information and generate motor outputs appropriate to their size and structure. Patterned sensory experience has long been known to induce various forms of developmental plasticity that ultimately shape mature neural circuits. These same types of plasticity also allow developing organisms to respond appropriately to the external world by dynamically adapting neural circuit function to ongoing changes in brain circuitry and sensory input. Recent work on the visual systems of frogs and fish has provided an unprecedented view into how visual experience dynamically affects circuit function at many levels, ranging from gene expression to network function... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3285828 Wed, 10 Feb 2010 00:00:00 +0100 3285828 http://www.medworm.com/index.php?rid=3255421&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20138673%26dopt%3DAbstract Authors: Chédotal A Cerebellar granule cells undergo profound and rapid morphological modifications during development while they migrate from their birthplace at the surface of the cerebellar cortex to its deepest layer. Post-mitotic granule cells extend bipolar axons and sequentially use the two main modes of migration, tangential and radial, to reach their final destinations. Recent studies show that protein degradation involving key cell-cycle regulators controls granule cell axon extension. The use of knockout mice deficient in different axon-guidance molecules combined with cutting-edge imaging methods has started to shed light on the molecular mechanisms that trigger granule cell migration. These studies suggest that a major reorganization of the cytoskeleton occurs as gran... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3255421 Fri, 05 Feb 2010 00:00:00 +0100 3255421 http://www.medworm.com/index.php?rid=3255422&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20138375%26dopt%3DAbstract Authors: Kasai H, Fukuda M, Watanabe S, Hayashi-Takagi A, Noguchi J Recent studies show that dendritic spines are dynamic structures. Their rapid creation, destruction and shape-changing are essential for short- and long-term plasticity at excitatory synapses on pyramidal neurons in the cerebral cortex. The onset of long-term potentiation, spine-volume growth and an increase in receptor trafficking are coincident, enabling a 'functional readout' of spine structure that links the age, size, strength and lifetime of a synapse. Spine dynamics are also implicated in long-term memory and cognition: intrinsic fluctuations in volume can explain synapse maintenance over long periods, and rapid, activity-triggered plasticity can relate directly to cognitive processes. Thus, spine dynamics are c... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3255422 Thu, 04 Feb 2010 00:00:00 +0100 3255422 http://www.medworm.com/index.php?rid=3179271&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20071039%26dopt%3DAbstract Authors: Burke SN, Barnes CA Excitatory synaptic transmission is altered during aging in hippocampal granule cells, and in CA3 and CA1 pyramidal cells. These functional changes contribute to age-associated impairments in experimentally-induced plasticity in each of these primary hippocampal subregions. In CA1, plasticity evoked by stimulation shares common mechanisms with the synaptic modification observed following natural behavior. Aging results in deficits in both artificially- and behaviorally-induced plasticity, and this could in part reflect age-related changes in Ca(2+) homeostasis. Other observations, however, suggest that increased intracellular Ca(2+) levels are beneficial under some circumstances. This review focuses on age-associated changes in synaptic function, how these ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3179271 Mon, 11 Jan 2010 00:00:00 +0100 3179271 http://www.medworm.com/index.php?rid=3164594&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20060600%26dopt%3DAbstract Authors: Cleland TA Sensory representations are repeatedly transformed by neural computations that determine which of their attributes can be effectively processed at each stage. Whereas some early computations are common across multiple sensory systems, they can utilize dissimilar underlying mechanisms depending on the properties of each modality. Recent work in the olfactory bulb has substantially clarified the neural algorithms underlying early odor processing. The high-dimensionality of odor space strictly limits the utility of topographical representations, forcing similarity-dependent computations such as decorrelation to employ unusual neural algorithms. The distinct architectures and properties of the two prominent computational layers in the olfactory bulb suggest that the bul... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3164594 Thu, 07 Jan 2010 00:00:00 +0100 3164594 http://www.medworm.com/index.php?rid=3143050&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20045200%26dopt%3DAbstract Authors: Aktas O, Kieseier B, Hartung HP Multiple sclerosis (MS), an incurable but manageable disorder, is characterized by chronic inflammatory demyelination and neurodegeneration in the central nervous system. Although the primary cause of this often devastating disease remains elusive, major therapeutic advances have occurred during the past two decades. Here, we present a review of current immunomodulatory treatments and outline upcoming therapy approaches, including biologics and oral alternatives that might have equivalent or superior efficacy and/or enhanced tolerability compared with available treatments, and discuss the scientific rationale and expected benefits and risks for these compounds. We also speculate about alternatives beyond immune-directed approaches, review novel ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3143050 Wed, 30 Dec 2009 00:00:00 +0100 3143050 http://www.medworm.com/index.php?rid=3143049&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20045201%26dopt%3DAbstract Authors: Panzeri S, Brunel N, Logothetis NK, Kayser C Determining how neuronal activity represents sensory information is central for understanding perception. Recent work shows that neural responses at different timescales can encode different stimulus attributes, resulting in a temporal multiplexing of sensory information. Multiplexing increases the encoding capacity of neural responses, enables disambiguation of stimuli that cannot be discriminated at a single response timescale, and makes sensory representations stable to the presence of variability in the sensory world. Thus, as we discuss here, temporal multiplexing could be a key strategy used by the brain to form an information-rich and stable representation of the environment. PMID: 20045201 [PubMed - as supplied by publis... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3143049 Wed, 30 Dec 2009 00:00:00 +0100 3143049 http://www.medworm.com/index.php?rid=3115536&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20022389%26dopt%3DAbstract Authors: Macvicar BA, Thompson RJ Pannexins are large-pore ion channels with broad expression in the central nervous system (CNS). The channels function by releasing large signaling molecules, such ATP and arachidonic acid derivatives, from neurons and possibly astrocytes. They might also contribute to novel forms of non-synaptic communication in the CNS, thereby affecting synaptic function, astrocytic Ca(2+) wave propagation and possibly regulation of vascular tone in the brain. Panx1 activation in various in vitro pathological conditions implicates these channels in ischemic, excitotoxic and ATP-dependent cell death, whereas Panx coupling with purinergic receptors triggers the inflammasome. Novel functions for the pannexin channels are likely to be discovered as current understanding... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3115536 Thu, 17 Dec 2009 00:00:00 +0100 3115536 http://www.medworm.com/index.php?rid=3067738&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19963289%26dopt%3DAbstract Authors: Hoeffer CA, Klann E Mammalian target of rapamycin (mTOR) is a protein kinase involved in translation control and long-lasting synaptic plasticity. mTOR functions as the central component of two multi-protein signaling complexes, mTORC1 and mTORC2, which can be distinguished from each other based on their unique compositions and substrates. Although the majority of evidence linking mTOR function to synaptic plasticity comes from studies utilizing rapamycin, studies in genetically modified mice also suggest that mTOR couples receptors to the translation machinery for establishing long-lasting synaptic changes that are the basis for higher order brain function, including long-term memory. Finally, perturbation of the mTOR signaling cascade appears to be a common pathophysiologica... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3067738 Fri, 04 Dec 2009 00:00:00 +0100 3067738 http://www.medworm.com/index.php?rid=3067737&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19963290%26dopt%3DAbstract Authors: Prager-Khoutorsky M, Bourque CW The proportional relation between circulating vasopressin concentration and plasma osmolality is fundamental for body fluid homeostasis. Although changes in the sensitivity of this relation are associated with pathophysiological conditions, central mechanisms modulating osmoregulatory gain are unknown. Here, we review recent data that sheds important light on this process. The cell autonomous osmosensitivity of vasopressin neurons depends on cation channels comprising a variant of the transient receptor potential vanilloid 1 (TRPV1) channel. Hyperosmotic activation is mediated by a mechanical process where sensitivity increases in proportion with actin filament density. Moreover, angiotensin II amplifies osmotic activation by a rapid stimulation... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3067737 Fri, 04 Dec 2009 00:00:00 +0100 3067737 http://www.medworm.com/index.php?rid=3057471&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19954851%26dopt%3DAbstract Authors: Schiff ND Recovery of consciousness following severe brain injuries can occur over long time intervals. Importantly, evolving cognitive recovery can be strongly dissociated from motor recovery in some individuals, resulting in underestimation of cognitive capacities. Common mechanisms of cerebral dysfunction that arise at the neuronal population level may explain slow functional recoveries from severe brain injuries. This review proposes a "mesocircuit" model that predicts specific roles for different structural and dynamic changes that may occur gradually during recovery. Recent functional neuroimaging studies that operationally identify varying levels of awareness, memory and other higher brain functions in patients with no behavioral evidence of these cognitive capacities a... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3057471 Mon, 30 Nov 2009 00:00:00 +0100 3057471 http://www.medworm.com/index.php?rid=3003594&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19914722%26dopt%3DAbstract Authors: Jarvis MF Chronic pain is characterized by enhanced sensory neurotransmission that underlies increased sensitivity to noxious stimuli and the perception of non-noxious stimuli as painful. Evidence from neurophysiological and pharmacological studies demonstrates that ATP produces pain by directly enhancing neuronal excitability via the activation of specific ligand-gated ion channels, the P2X3 and P2X2/3 receptors. In addition, ATP activates CNS glial cells (e.g. microglia) in response to persistent nociceptive stimulation. This latter effect involves several distinct receptor-mediated signaling pathways linked to the P2X4, P2X7 and P2Y(12) receptors. This review summarizes new data that places these purinergic signaling events in a mechanistic context that illustrates the abil... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=3003594 Fri, 13 Nov 2009 00:00:00 +0100 3003594 http://www.medworm.com/index.php?rid=2992942&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19906448%26dopt%3DAbstract Authors: Szaro BG, Strong MJ Neurofilament (NF) protein expression is coupled to axon development and the maintenance of neuronal homeostasis. Here, we present evidence that this tight regulation depends critically on post-transcriptionally regulated changes in NF mRNA transport, translation and stability. Recent studies have shown that post-transcriptional mechanisms modulate increases in NF gene transcription during axon regeneration to yield the final pattern of NF protein expression. Other recent work has found that post-transcriptional control of NFs shares elements with that of other axonal proteins and that its dysregulation contributes to amyotrophic lateral sclerosis. Such studies herald a novel approach to understanding how neurons coordinate the expressions of functionally r... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2992942 Mon, 09 Nov 2009 00:00:00 +0100 2992942 http://www.medworm.com/index.php?rid=2968654&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19889466%26dopt%3DAbstract Authors: Mozzachiodi R, Byrne JH Decades of research on the cellular mechanisms of memory have led to the widely held view that memories are stored as modifications of synaptic strength. These changes involve presynaptic processes, such as direct modulation of the release machinery, or postsynaptic processes, such as modulation of receptor properties. Parallel studies have revealed that memories might also be stored by nonsynaptic processes, such as modulation of voltage-dependent membrane conductances, which are expressed as changes in neuronal excitability. Although in some cases nonsynaptic changes can function as part of the engram itself, they might also serve as mechanisms through which a neural circuit is set to a permissive state to facilitate synaptic modifications that are ne... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2968654 Mon, 02 Nov 2009 00:00:00 +0100 2968654 http://www.medworm.com/index.php?rid=2912914&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19837469%26dopt%3DAbstract Authors: Heng JI, Chariot A, Nguyen L During neural development, the cytoskeleton of newborn neurons undergoes extensive and dynamic remodelling to facilitate the sequential steps of neurogenesis, cell migration and terminal differentiation. It is clear from studying the mechanisms that precipitate these functions that different configurations of the cytoskeleton prefigure the correct execution of each step and define cohorts of proteins the functions of which are indispensable for the control of neuronal migration but not terminal differentiation. These combinatorial protein functions are also predetermined by regulated gene expression and the precise subcellular localisation of their protein products. Here, we expand on this view in the context of recent data on how the cytoskeleton ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2912914 Thu, 15 Oct 2009 23:00:00 +0100 2912914 http://www.medworm.com/index.php?rid=2888000&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19819033%26dopt%3DAbstract Authors: Bogacz R, Wagenmakers EJ, Forstmann BU, Nieuwenhuis S In many situations, decision makers need to negotiate between the competing demands of response speed and response accuracy, a dilemma generally known as the speed-accuracy tradeoff (SAT). Despite the ubiquity of SAT, the question of how neural decision circuits implement SAT has received little attention up until a year ago. We review recent studies that show SAT is modulated in association and pre-motor areas rather than in sensory or primary motor areas. Furthermore, the studies suggest that emphasis on response speed increases the baseline firing rate of cortical integrator neurons. We also review current theories on how and where in the brain the SAT is controlled, and we end by proposing research directions that could... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2888000 Wed, 07 Oct 2009 23:00:00 +0100 2888000 http://www.medworm.com/index.php?rid=2859308&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19796831%26dopt%3DAbstract Authors: Kehoe PG, Miners S, Love S The renin-angiotensin system (RAS) is an important regulator of blood pressure. Observational and experimental studies suggest that alterations in blood pressure and components of the brain RAS contribute to the development and progression of Alzheimer's disease (AD), resulting in changes that can lead or contribute to cognitive decline. The complexity of the RAS and diversity of its interactions with neurological processes have recently become apparent but large gaps in our understanding still remain. Modulation of activity of components of the brain RAS offers substantial opportunities for the treatment and prevention of dementia, including AD. This paper reviews molecular, genetic, experimental and clinical data as well as the therapeutic opportun... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2859308 Mon, 28 Sep 2009 23:00:00 +0100 2859308 http://www.medworm.com/index.php?rid=2839651&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19782409%26dopt%3DAbstract Authors: Jessberger S, Gage FH, Eisch AJ, Lagace DC Cyclin-dependent kinase 5 (Cdk5) has been implicated in the migration, maturation and survival of neurons born during embryonic development. New evidence suggests that Cdk5 has comparable but also distinct functions in adult neurogenesis. Here we summarize accumulating evidence on the role of Cdk5 in regulation of the cell cycle, migration, survival, maturation and neuronal integration. We specifically highlight the many similarities and few tantalizing differences in the roles of Cdk5 in the embryonic and adult brain. We discuss the signaling pathways that might contribute to Cdk5 action in regulating embryonic and adult neurogenesis, highlighting future research directions that will help to clarify the mechanisms underlying lifelong... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2839651 Wed, 23 Sep 2009 23:00:00 +0100 2839651 http://www.medworm.com/index.php?rid=2839650&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19782410%26dopt%3DAbstract Authors: Barbey AK, Krueger F, Grafman J Recent progress in cognitive neuroscience highlights the involvement of the prefrontal cortex (PFC) in social cognition. Accumulating evidence demonstrates that representations within the lateral PFC enable people to coordinate their thoughts and actions with their intentions to support goal-directed social behavior. Despite the importance of this region in guiding social interactions, remarkably little is known about the functional organization and forms of social inference processed by the lateral PFC. Here, we introduce a cognitive neuroscience framework for understanding the inferential architecture of the lateral PFC, drawing upon recent theoretical developments in evolutionary psychology and emerging neuroscience evidence about how this re... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2839650 Wed, 23 Sep 2009 23:00:00 +0100 2839650 http://www.medworm.com/index.php?rid=2839649&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19782411%26dopt%3DAbstract This article reviews developments in the signaling mechanisms that regulate specific aspects of reactive astrogliosis and highlights the potential to identify novel therapeutic molecular targets for diverse neurological disorders. PMID: 19782411 [PubMed - as supplied by publisher] (Source: Trends in Neurosciences) Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2839649 Wed, 23 Sep 2009 23:00:00 +0100 2839649 http://www.medworm.com/index.php?rid=2839654&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19781792%26dopt%3DAbstract We describe work on the role of the calcium- and voltage-gated BK channel in alcohol tolerance, highlighting the lipid environment, BK protein isoform selection and auxiliary BK channel proteins. We show how ethanol, which had the reputation of a nonspecific membrane perturbant, is now being examined at realistic concentrations with cutting-edge techniques, providing novel molecular targets for therapeutic approaches to alcoholism. Addictive disorders impact our emotional, physical and financial status, and burden our healthcare system. Although alcohol is the focus of this review, it is highly probable, given the common neural and biochemical pathways used by drugs of abuse, that the findings described here will also apply to other drugs. PMID: 19781792 [PubMed - as supplied by publis... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2839654 Tue, 22 Sep 2009 23:00:00 +0100 2839654 http://www.medworm.com/index.php?rid=2839653&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19781793%26dopt%3DAbstract We describe a recently identified mechanism of neuronal plasticity in primary afferent nociceptive nerve fibers (nociceptors) by which an acute inflammatory insult or environmental stressor can trigger long-lasting hypersensitivity of nociceptors to inflammatory cytokines. This phenomenon, "hyperalgesic priming," depends on the epsilon isoform of protein kinase C (PKCvarepsilon) and a switch in intracellular signaling pathways that mediate cytokine-induced nociceptor hyperexcitability. We discuss the impact of this discovery on our understanding of, and ultimately our ability to treat, a variety of enigmatic and debilitating pain conditions, including those associated with repetitive injury, and generalized pain conditions, such as fibromyalgia. PMID: 19781793 [PubMed - as supplied by ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2839653 Tue, 22 Sep 2009 23:00:00 +0100 2839653 http://www.medworm.com/index.php?rid=2839652&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19781794%26dopt%3DAbstract Authors: Cole MW, Yeung N, Freiwald WA, Botvinick M Cognitive neuroscience research relies, in part, on homologies between the brains of human and non-human primates. A quandary therefore arises when presumed anatomical homologues exhibit different functional properties. Such a situation has recently arisen in the case of the anterior cingulate cortex (ACC). In humans, numerous studies suggest a role for ACC in detecting conflicts in information processing. Studies of macaque monkey ACC, in contrast, have failed to find conflict-related responses. We consider several interpretations of this discrepancy, including differences in research methodology and cross-species differences in functional neuroanatomy. New directions for future research are outlined, emphasizing the importance of di... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2839652 Tue, 22 Sep 2009 23:00:00 +0100 2839652 http://www.medworm.com/index.php?rid=2832550&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19775759%26dopt%3DAbstract Authors: Chuang DM, Leng Y, Marinova Z, Kim HJ, Chiu CT Histone deacetylases (HDACs) play a key role in homeostasis of protein acetylation in histones and other proteins and in regulating fundamental cellular activities such as transcription. A wide range of brain disorders are associated with imbalances in protein acetylation levels and transcriptional dysfunctions. Treatment with various HDAC inhibitors can correct these deficiencies and has emerged as a promising new strategy for therapeutic intervention in neurodegenerative disease. Here, we review and discuss intriguing recent developments in the use of HDAC inhibitors to combat neurodegenerative conditions in cellular and disease models. HDAC inhibitors have neuroprotective, neurotrophic and anti-inflammatory properties; improvem... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2832550 Sun, 20 Sep 2009 23:00:00 +0100 2832550 http://www.medworm.com/index.php?rid=2824905&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19765834%26dopt%3DAbstract Authors: Valjent E, Bertran-Gonzalez J, Hervé D, Fisone G, Girault JA Understanding how molecular signaling pathways participate in behavioral responses requires determining precisely in which neuronal populations they are activated. The recent development of bacterial artificial chromosome (BAC) transgenic mice expressing a variety of reporters, epitope tagged-proteins or Cre recombinase driven by specific promoters, is a significant step forward in this direction. These mice help overcome the limitations of traditional approaches that examine an average of signaling events occurring in mixed populations of cells. Here, we review how recent studies using such tools have revisited the regulation of striatal signaling pathways, demonstrating the striking segregation between neurons... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2824905 Tue, 15 Sep 2009 23:00:00 +0100 2824905 http://www.medworm.com/index.php?rid=2824904&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19765835%26dopt%3DAbstract Authors: Eidelberg D Network analysis of functional brain imaging data is an innovative approach to study circuit abnormalities in neurodegenerative diseases. In Parkinson's disease, spatial covariance analysis of resting-state metabolic images has identified specific regional patterns associated with motor and cognitive symptoms. With functional imaging, these metabolic networks have recently been used to measure system-related progression and to evaluate novel treatment strategies. Network analysis is also being used to characterize specific functional biomarkers for Huntington's disease and Alzheimer's disease. These networks have been particularly helpful in uncovering compensatory mechanisms in genetically at-risk individuals. Ongoing developments in network applications are likel... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2824904 Tue, 15 Sep 2009 23:00:00 +0100 2824904 http://www.medworm.com/index.php?rid=2805144&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19758713%26dopt%3DAbstract Authors: Restrepo D, Doucette W, Whitesell JD, McTavish TS, Salcedo E Animals that depend on smell for communication and survival extract multiple pieces of information from a single complex odor. Mice can collect information on sex, genotype, health and dietary status from urine scent marks, a stimulus made up of hundreds of molecules. This ability is all the more remarkable considering that natural odors are encountered against varying olfactory backgrounds; the olfactory system must therefore provide some mechanism for extracting the most relevant information. Here we discuss recent data indicating that the readout of olfactory input by mitral cells in the olfactory bulb can be modified by behavioral context. We speculate that the olfactory cortex plays a key role in tuning the read... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2805144 Sun, 13 Sep 2009 23:00:00 +0100 2805144 http://www.medworm.com/index.php?rid=2805143&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19758714%26dopt%3DAbstract Authors: Wise RA Forebrain dopamine circuitry has traditionally been studied by two largely independent specialist groups: students of Parkinson's disease who study the nigrostriatal dopamine system that originates in the substantia nigra (SN), and students of motivation and addiction who study the role of the mesolimbic and mesocortical dopamine systems that originate in the ventral tegmental area (VTA). The anatomical evidence for independent nigrostriatal and mesolimbic dopamine systems has, however, long been obsolete. There is now compelling evidence that both nominal "systems" participate in reward function and addiction. Electrical stimulation of both SN and VTA is rewarding, blockade of glutamatergic or cholinergic input to either SN or VTA attenuates the habit-forming effects ... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2805143 Sun, 13 Sep 2009 23:00:00 +0100 2805143 http://www.medworm.com/index.php?rid=2800065&cid=s_36145_168_f&fid=36145&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19748686%26dopt%3DAbstract Authors: Zhang P, Lathia JD, Flavahan WA, Rich JN, Mattson MP Glioblastoma brain tumors harbor a small population of cancer stem cells that are resistant to conventional chemotherapeutic and radiation treatments, and are believed responsible for tumor recurrence and mortality. The identification of the epigenetic molecular mechanisms that control self-renewal of glioblastoma stem cells will foster development of targeted therapeutic approaches. The transcriptional repressor REST, best known for its role in controlling cell fate decisions in neural progenitor cells, may also be crucial for cancer stem cell self-renewal. Two novel mechanisms for regulating the stability of REST have recently been revealed: these involve the telomere-binding protein TRF2 and the ubiquitin E3 ligase SCFbet... Trends in Neurosciences journals http://www.medworm.com/rss/comments.php?id=2800065 Thu, 10 Sep 2009 23:00:00 +0100 2800065