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278 records returned

The neural-glial purinergic receptor ensemble in chronic pain states.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Neurosciences - November 13, 2009 Category: Neuroscience Authors: Jarvis MF Tags: Trends Neurosci Source Type: journals

Post-transcriptional control of neurofilaments: New roles in development, regeneration and neurodegenerative disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Neurosciences - November 9, 2009 Category: Neuroscience Authors: Szaro BG, Strong MJ Tags: Trends Neurosci Source Type: journals

More than synaptic plasticity: role of nonsynaptic plasticity in learning and memory.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 mi...
Source: Trends in Neurosciences - November 2, 2009 Category: Neuroscience Authors: Mozzachiodi R, Byrne JH Tags: Trends Neurosci Source Type: journals

Molecular layers underlying cytoskeletal remodelling during cortical development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 sub...
Source: Trends in Neurosciences - October 15, 2009 Category: Neuroscience Authors: Heng JI, Chariot A, Nguyen L Tags: Trends Neurosci Source Type: journals

The neural basis of the speed-accuracy tradeoff.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Neurosciences - October 7, 2009 Category: Neuroscience Authors: Bogacz R, Wagenmakers EJ, Forstmann BU, Nieuwenhuis S Tags: Trends Neurosci Source Type: journals

Angiotensins in Alzheimer's disease - friend or foe?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 preventio...
Source: Trends in Neurosciences - September 28, 2009 Category: Neuroscience Authors: Kehoe PG, Miners S, Love S Tags: Trends Neurosci Source Type: journals

Making a neuron: Cdk5 in embryonic and adult neurogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ad...
Source: Trends in Neurosciences - September 23, 2009 Category: Neuroscience Authors: Jessberger S, Gage FH, Eisch AJ, Lagace DC Tags: Trends Neurosci Source Type: journals

An evolutionarily adaptive neural architecture for social reasoning.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Neurosciences - September 23, 2009 Category: Neuroscience Authors: Barbey AK, Krueger F, Grafman J Tags: Trends Neurosci Source Type: journals

Molecular dissection of reactive astrogliosis and glial scar formation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Trends in Neurosciences - September 23, 2009 Category: Neuroscience Authors: Sofroniew MV Tags: Trends Neurosci Source Type: journals

BK Channels: mediators and models for alcohol tolerance.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 n...
Source: Trends in Neurosciences - September 22, 2009 Category: Neuroscience Authors: Treistman SN, Martin GE Tags: Trends Neurosci Source Type: journals

Critical role of nociceptor plasticity in chronic pain.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 debilitati...
Source: Trends in Neurosciences - September 22, 2009 Category: Neuroscience Authors: Reichling DB, Levine JD Tags: Trends Neurosci Source Type: journals

Cingulate cortex: Diverging data from humans and monkeys.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 dif...
Source: Trends in Neurosciences - September 22, 2009 Category: Neuroscience Authors: Cole MW, Yeung N, Freiwald WA, Botvinick M Tags: Trends Neurosci Source Type: journals

Multiple roles of HDAC inhibition in neurodegenerative conditions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Trends in Neurosciences - September 20, 2009 Category: Neuroscience Authors: Chuang DM, Leng Y, Marinova Z, Kim HJ, Chiu CT Tags: Trends Neurosci Source Type: journals

Looking BAC at striatal signaling: cell-specific analysis in new transgenic mice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 re...
Source: Trends in Neurosciences - September 15, 2009 Category: Neuroscience Authors: Valjent E, Bertran-Gonzalez J, Hervé D, Fisone G, Girault JA Tags: Trends Neurosci Source Type: journals

Metabolic brain networks in neurodegenerative disorders: a functional imaging approach.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Neurosciences - September 15, 2009 Category: Neuroscience Authors: Eidelberg D Tags: Trends Neurosci Source Type: journals

From the top down: flexible reading of a fragmented odor map.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 modifi...
Source: Trends in Neurosciences - September 13, 2009 Category: Neuroscience Authors: Restrepo D, Doucette W, Whitesell JD, McTavish TS, Salcedo E Tags: Trends Neurosci Source Type: journals

Roles for nigrostriatal-not just mesocorticolimbic-dopamine in reward and addiction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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. Electri...
Source: Trends in Neurosciences - September 13, 2009 Category: Neuroscience Authors: Wise RA Tags: Trends Neurosci Source Type: journals

Squelching glioblastoma stem cells by targeting REST for proteasomal degradation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 hav...
Source: Trends in Neurosciences - September 10, 2009 Category: Neuroscience Authors: Zhang P, Lathia JD, Flavahan WA, Rich JN, Mattson MP Tags: Trends Neurosci Source Type: journals

Glutamate synapse in developing brain: an integrative perspective beyond the silent state.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cellular events underlying the establishment of glutamate transmission have been the focus of attention because appropriate wiring of developing neuronal networks is essential for adult brain functions. Although establishment of a synapse is a dynamic process requiring axonal and dendritic refinements, the functional interplay between pre- and postsynaptic signaling is often ignored. Here, we discuss recent data on pre- and postsynaptic plasticity of the glutamate synapse in the developing brain. The key aspect of the proposed model is that developing synapses are functionally labile in response to activity and this la...
Source: Trends in Neurosciences - September 3, 2009 Category: Neuroscience Authors: Hanse E, Taira T, Lauri S, Groc L Tags: Trends Neurosci Source Type: journals

Visual processing, learning and feedback in the primate eye movement system.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We present an overview of recent paradigms used for studying visual information and reward processing in the human and monkey oculomotor pathways. Current evidence indicates that eye movements made during visual search tasks rely on neural computations similar to those employed when eye movements are planned and executed to obtain explicit rewards. These data suggest that human eye movements originate from the processing of (predominantly visual) sensory information, feedback about previous errors, and expectations about factors, such as reward. We conclude that these properties make the saccadic system an ideal model for ...
Source: Trends in Neurosciences - August 31, 2009 Category: Neuroscience Authors: Trommershäuser J, Glimcher PW, Gegenfurtner KR Tags: Trends Neurosci Source Type: journals

Animal consciousness: a synthetic approach.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Despite anecdotal evidence suggesting conscious states in a variety of non-human animals, no systematic neuroscientific investigation of animal consciousness has yet been undertaken. We set forth a framework for such an investigation that incorporates integration of data from neuroanatomy, neurophysiology, and behavioral studies, uses evidence from humans as a benchmark, and recognizes the critical role of explicit verbal report of conscious experiences in human studies. We illustrate our framework with reference to two subphyla: one relatively near to mammals - birds - and one quite far -cephalopod molluscs. Consisten...
Source: Trends in Neurosciences - August 25, 2009 Category: Neuroscience Authors: Edelman DB, Seth AK Tags: Trends Neurosci Source Type: journals

Microsaccades: a neurophysiological analysis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Microsaccades are the largest and fastest of the fixational eye movements, which are involuntary eye movements produced during attempted visual fixation. In recent years, the interaction between microsaccades, perception and cognition has become one of the most rapidly growing areas of study in visual neuroscience. The neurophysiological consequences of microsaccades have been the focus of less attention, however, as have the oculomotor mechanisms that generate and control microsaccades. Here we review the latest neurophysiological findings concerning microsaccades and discuss their relationships to perception and cogn...
Source: Trends in Neurosciences - August 25, 2009 Category: Neuroscience Authors: Martinez-Conde S, Macknik SL, Troncoso XG, Hubel DH Tags: Trends Neurosci Source Type: journals

Air pollution: mechanisms of neuroinflammation and CNS disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Air pollution has been implicated as a chronic source of neuroinflammation and reactive oxygen species (ROS) that produce neuropathology and central nervous system (CNS) disease. Stroke incidence and Alzheimer's and Parkinson's disease pathology are linked to air pollution. Recent reports reveal that air pollution components reach the brain; systemic effects that impact lung and cardiovascular disease also impinge upon CNS health. While mechanisms driving air pollution-induced CNS pathology are poorly understood, new evidence suggests that microglial activation and changes in the blood-brain barrier are key components....
Source: Trends in Neurosciences - August 25, 2009 Category: Neuroscience Authors: Block ML, Calderón-Garcidueñas L Tags: Trends Neurosci Source Type: journals

Neurodevelopmental mechanisms of schizophrenia: understanding disturbed postnatal brain maturation through neuregulin-1-ErbB4 and DISC1.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Schizophrenia (SZ) is primarily an adult psychiatric disorder in which disturbances caused by susceptibility genes and environmental insults during early neurodevelopment initiate neurophysiological changes over a long time course, culminating in the onset of full-blown disease nearly two decades later. Aberrant postnatal brain maturation is an essential mechanism underlying the disease. Currently, symptoms of SZ are treated with anti-psychotic medications that have variable efficacy and severe side effects. There has been much interest in the prodromal phase and the possibility of preventing SZ by interfering with the...
Source: Trends in Neurosciences - August 24, 2009 Category: Neuroscience Authors: Jaaro-Peled H, Hayashi-Takagi A, Seshadri S, Kamiya A, Brandon NJ, Sawa A Tags: Trends Neurosci Source Type: journals

From selective vulnerability to connectivity: insights from newborn brain imaging.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The ability to image the newborn brain during development has provided new information regarding the effects of injury on brain development at different vulnerable time periods. Studies in animal models of brain injury correlate beautifully with what is now observed in the human newborn. We now know that injury at term primarily results in grey matter injury while injury in the premature brain predominantly results in a pattern of white matter injury, though recent evidence suggests a blurring of this distinction . These injuries affect how the brain matures subsequently and again, imaging has led to new insights that ...
Source: Trends in Neurosciences - August 24, 2009 Category: Neuroscience Authors: Miller SP, Ferriero DM Tags: Trends Neurosci Source Type: journals

Functional versatility of transcription factors in the nervous system: the SRF paradigm.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Individual transcription factors in the brain frequently display broad functional versatility, thereby controlling multiple cellular outputs. In accordance, neuron-restricted mutagenesis of the murine Srf gene, encoding the transcription factor serum response factor (SRF), revealed numerous SRF functions in the nervous system. First, SRF controls immediate early gene (IEG) activation associated with perception of synaptic activity, learning and memory. Second, processes linked to actin cytoskeletal dynamics are mediated by SRF, such as developmental neuronal migration, outgrowth and pathfinding of neurites, as well as ...
Source: Trends in Neurosciences - July 27, 2009 Category: Neuroscience Authors: Knöll B, Nordheim A Tags: Trends Neurosci Source Type: journals

Recent insights into the molecular genetics of dementia.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Our understanding of the molecular genetic basis of two common neurodegenerative dementias, Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), has greatly advanced in recent years. Progranulin mutations were identified as a major cause of FTLD and a potential susceptibility factor for other forms of dementia. In addition, through copy-number analyses of previously identified disease genes and the study of microRNA regulation in dementia, new evidence emerged to support the view that subtle variability in the expression of known disease proteins could increase the risk for sporadic forms of dementia....
Source: Trends in Neurosciences - July 26, 2009 Category: Neuroscience Authors: Rademakers R, Rovelet-Lecrux A Tags: Trends Neurosci Source Type: journals

Reconsolidation: maintaining memory relevance.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The retrieval of a memory places it into a plastic state, the result of which is that the memory can be disrupted or even enhanced by experimental treatment. This phenomenon has been conceptualised within a framework of memories being reactivated and then reconsolidated in repeated rounds of cellular processing. The reconsolidation phase has been seized upon as crucial for the understanding of memory stability and, more recently, as a potential therapeutic target in the treatment of disorders such as post-traumatic stress and drug addiction. However, little is known about the reactivation process, or what might be the ...
Source: Trends in Neurosciences - July 26, 2009 Category: Neuroscience Authors: Lee JL Tags: Trends Neurosci Source Type: journals

Neocortical neurogenesis: morphogenetic gradients and beyond.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Each of the five cellular layers of the cerebral neocortex is composed of a specific number of a single predominant 'class' of projection neuron. The projection neuron class is defined by its unique morphology and axonal projections to other areas of the brain. Precursor cell populations lining the embryonic lateral ventricles produce the projection neurons. The mechanisms regulating precursor cell proliferation also regulate total numbers of neurons produced at specific developmental periods and destined to a specific neocortical layer. Because the newborn neurons migrate relatively long distances to reach their final...
Source: Trends in Neurosciences - July 24, 2009 Category: Neuroscience Authors: Caviness VS, Nowakowski RS, Bhide PG Tags: Trends Neurosci Source Type: journals

Tripartite synapses: astrocytes process and control synaptic information.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The term 'tripartite synapse' refers to a concept in synaptic physiology based on the demonstration of the existence of bidirectional communication between astrocytes and neurons. Consistent with this concept, in addition to the classic 'bipartite' information flow between the pre- and postsynaptic neurons, astrocytes exchange information with the synaptic neuronal elements, responding to synaptic activity and, in turn, regulating synaptic transmission. Because recent evidence has demonstrated that astrocytes integrate and process synaptic information and control synaptic transmission and plasticity, astrocytes, being ...
Source: Trends in Neurosciences - July 14, 2009 Category: Neuroscience Authors: Perea G, Navarrete M, Araque A Tags: Trends Neurosci Source Type: journals

Feature detection and the hypercomplex property in insects.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Discerning a target amongst visual 'clutter' is a complicated task that has been elegantly solved by flying insects, as evidenced by their mid-air interactions with conspecifics and prey. The neurophysiology of small-target motion detectors (STMDs) underlying these complex behaviors has recently been described and suggests that insects use mechanisms similar to those of hypercomplex cells of the mammalian visual cortex to achieve target-specific tuning. Cortical hypercomplex cells are end-stopped, which means that they respond optimally to small moving targets, with responses to extended bars attenuated. We review not ...
Source: Trends in Neurosciences - June 18, 2009 Category: Neuroscience Authors: Nordström K, O'Carroll DC Tags: Trends Neurosci Source Type: journals

The emerging role of synaptic cell-adhesion pathways in the pathogenesis of autism spectrum disorders.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent advances in genetics and genomics have unveiled numerous cases of autism spectrum disorders (ASDs) associated with rare, causal genetic variations. These findings support a novel view of ASDs in which many independent, individually rare genetic variants, each associated with a very high relative risk, together explain a large proportion of ASDs. Although these rare variants impact diverse pathways, there is accumulating evidence that synaptic pathways, including those involving synaptic cell adhesion, are disrupted in some subjects with ASD. These findings provide insights into the pathogenesis of ASDs and enabl...
Source: Trends in Neurosciences - June 18, 2009 Category: Neuroscience Authors: Betancur C, Sakurai T, Buxbaum JD Tags: Trends Neurosci Source Type: journals

Nucleocytoplasmic protein shuttling: the direct route in synapse-to-nucleus signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In neurons multiple signaling pathways converge in the nucleus to regulate the expression of genes associated with long-term structural changes of synapto-dendritic input. Of pivotal importance for this type of transcriptional regulation is synapse-to-nucleus communication. Several studies suggest that the nuclear transport of proteins from synapses is involved in this signaling process, including evidence that synapses contain proteins with nuclear localization sequences and components of the nuclear import machinery. Here, we review the evidence for synapse-to-nucleus signaling by means of retrograde transport of pro...
Source: Trends in Neurosciences - June 10, 2009 Category: Neuroscience Authors: Jordan BA, Kreutz MR Tags: Trends Neurosci Source Type: journals

Immune senescence and brain aging: can rejuvenation of immunity reverse memory loss?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The factors that determine brain aging remain a mystery. Do brain aging and memory loss reflect processes occurring only within the brain? Here, we present a novel view, linking aging of adaptive immunity to brain senescence and specifically to spatial memory deterioration. Inborn immune deficiency, in addition to sudden imposition of immune malfunction in young animals, results in cognitive impairment. As a corollary, immune restoration at adulthood or in the elderly results in a reversal of memory loss. These results, together with the known deterioration of adaptive immunity in the elderly, suggest that memory loss ...
Source: Trends in Neurosciences - June 8, 2009 Category: Neuroscience Authors: Ron-Harel N, Schwartz M Tags: Trends Neurosci Source Type: journals

Convergence and divergence in a neural architecture for recognition and memory.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
How does the brain represent external reality so that it can be perceived in the form of mental images? How are the representations stored in memory so that an approximation of their original content can be re-experienced during recall? A framework introduced in the late 1980s proposed that mental images arise from neural activity in early sensory cortices both during perception and recall. Neurons in the association cortices, by contrast, would not code explicit mental content; rather, they would hold the records needed to reconstruct an approximation of the original perceptual maps in early cortices. Several neurophy...
Source: Trends in Neurosciences - June 8, 2009 Category: Neuroscience Authors: Meyer K, Damasio A Tags: Trends Neurosci Source Type: journals

Common astrocytic programs during brain development, injury and cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In addition to radial glial cells of neurohistogenesis, immature astrocytes with stem-cell-like properties cordon off emerging functional patterns in the developing brain. Astrocytes also can be stem cells during adult neurogenesis, and a proposed potency of injury-associated reactive astrocytes has recently been substantiated. Astrocytic cells might additionally be involved in cancer stem cell-associated gliomagenesis. Thus, there are distinguishing roles for stem-cell-like astrocytes during brain development, in neurogenic niches in the adult, during attempted reactive neurogenesis after brain injury or disease and d...
Source: Trends in Neurosciences - May 31, 2009 Category: Neuroscience Authors: Silver DJ, Steindler DA Tags: Trends Neurosci Source Type: journals

The hippocampal rate code: anatomy, physiology and theory.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Since the days of Cajal, the CA1 pyramidal cell has arguably received more attention than any other neuron in the mammalian brain. Hippocampal CA1 pyramidal cells fire spikes with remarkable spatial and temporal precision, giving rise to the hippocampal rate and temporal codes. However, little is known about how different inputs interact during spatial behavior to generate such robust firing patterns. Here, we review the properties of the rodent hippocampal rate code and synthesize work from several disciplines to understand the functional anatomy and excitation-inhibition balance that can produce the rate-coded output...
Source: Trends in Neurosciences - May 31, 2009 Category: Neuroscience Authors: Ahmed OJ, Mehta MR Tags: Trends Neurosci Source Type: journals

From high anxiety trait to depression: a neurocognitive hypothesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although exposure to substantial stress has a major impact on the development of depression, there is considerable variability in the susceptibility of individuals to the adverse effects of stress. The personality trait of high anxiety has been identified as a vulnerability factor to develop depression. We propose here a new unifying model based on a series of neurocognitive mechanisms (and fed with crucial information provided by research on the fields of emotion, stress and cognition) whereby individuals presenting a high anxiety trait are particularly vulnerable to develop depression when facing stress and adversity...
Source: Trends in Neurosciences - May 31, 2009 Category: Neuroscience Authors: Sandi C, Richter-Levin G Tags: Trends Neurosci Source Type: journals

Modeling cognitive endophenotypes of schizophrenia in mice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Schizophrenia is a complex mental disorder that is still characterized by its symptoms rather than by biological markers because we have only a limited knowledge of its underlying molecular basis. In the past two decades, however, technical advances in genetics and brain imaging have provided new insights into the biology of the disease. Based on these advances we are now in a position to develop animal models that can be used to test specific hypotheses of the disease and explore mechanisms of pathogenesis. Here, we consider some of the insights that have emerged from studying in mice the relationship between defined ...
Source: Trends in Neurosciences - May 31, 2009 Category: Neuroscience Authors: Kellendonk C, Simpson EH, Kandel ER Tags: Trends Neurosci Source Type: journals

No NO, no pain? The role of nitric oxide and cGMP in spinal pain processing.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A large body of evidence indicates that nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) essentially contribute to the processing of nociceptive signals in the spinal cord. Many animal studies have unanimously shown that inhibition of NO or cGMP synthesis can considerably reduce both inflammatory and neuropathic pain. However, experiments with NO donors and cGMP analogs also caused conflicting results because dual pronociceptive and antinociceptive effects of these molecules have been observed. Here, we summarize the most recent advances in the understanding of NO- and cGMP-dependent signaling pathways in th...
Source: Trends in Neurosciences - May 31, 2009 Category: Neuroscience Authors: Schmidtko A, Tegeder I, Geisslinger G Tags: Trends Neurosci Source Type: journals

Associative learning and the genetics of schizophrenia.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Several well-validated susceptibility genes for schizophrenia have now been identified. We suggest that these genes can be divided into two broad classes. Those in the first class have direct effects on synaptic plasticity mediated through actions at glutamatergic synapses; those in the second class impact on meso-limbic dopamine signalling. We argue that these genes have an interactive effect on risk for psychosis and that this interaction can be understood in the context of associative learning theory. We illustrate how genetic variation in genes from these classes can contribute to the development of psychosis using...
Source: Trends in Neurosciences - May 31, 2009 Category: Neuroscience Authors: Hall J, Romaniuk L, McIntosh AM, Steele JD, Johnstone EC, Lawrie SM Tags: Trends Neurosci Source Type: journals

Functional imaging of the human dopaminergic midbrain.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Invasive recording of dopamine neurons in the substantia nigra and ventral tegmental area (SN/VTA) of behaving animals suggests a role for these neurons in reward learning and novelty processing. In humans, functional magnetic resonance imaging (fMRI) is currently the only non-invasive event-related method to measure SN/VTA activity, but it is debated to what extent fMRI enables inference about dopaminergic responses within the SN/VTA. We consider the anatomical and functional parcellation of the primate SN/VTA and find that its homogeneity suggests little variation in the regional specificity of fMRI signals for rewar...
Source: Trends in Neurosciences - May 31, 2009 Category: Neuroscience Authors: Düzel E, Bunzeck N, Guitart-Masip M, Wittmann B, Schott BH, Tobler PN Tags: Trends Neurosci Source Type: journals

Exercise and the brain: something to chew on.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Evidence is accumulating that exercise has profound benefits for brain function. Physical activity improves learning and memory in humans and animals. Moreover, an active lifestyle might prevent or delay loss of cognitive function with aging or neurodegenerative disease. Recent research indicates that the effects of exercise on the brain can be enhanced by concurrent consumption of natural products such as omega fatty acids or plant polyphenols. The potential synergy between diet and exercise could involve common cellular pathways important for neurogenesis, cell survival, synaptic plasticity and vascular function. Opt...
Source: Trends in Neurosciences - April 30, 2009 Category: Neuroscience Authors: van Praag H Tags: Trends Neurosci Source Type: journals

Purinergic signalling in autonomic control.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Intercellular purinergic signalling, which utilizes ATP as a transmitter, is fundamental for the operation of the autonomic nervous system. ATP is released together with 'classical' transmitters from sympathetic and parasympathetic nerves supplying various peripheral targets, modulates neurotransmission in autonomic ganglia, has an important role in local enteric neural control and coordination of intestinal secretion and motility, and acts as a common mediator for several distinct sensory modalities. Recently, the role of ATP-mediated signalling in the central nervous control of autonomic function has been addressed. ...
Source: Trends in Neurosciences - April 30, 2009 Category: Neuroscience Authors: Gourine AV, Wood JD, Burnstock G Tags: Trends Neurosci Source Type: journals

Decision by division: making cortical maps.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In the past three decades, mounting evidence has revealed that specification of the basic cortical neuronal classes starts at the time of their final mitotic divisions in the embryonic proliferative zones. This early cell determination continues during the migration of the newborn neurons across the widening cerebral wall, and it is in the cortical plate that they attain their final positions and establish species-specific cytoarchitectonic areas. Here, the development and evolutionary expansion of the neocortex is viewed in the context of the radial unit and protomap hypotheses. A broad spectrum of findings gave insig...
Source: Trends in Neurosciences - April 30, 2009 Category: Neuroscience Authors: Rakic P, Ayoub AE, Breunig JJ, Dominguez MH Tags: Trends Neurosci Source Type: journals

MRI in small brains displaying extensive plasticity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Manganese-enhanced magnetic resonance imaging (ME-MRI), blood oxygen-level-dependent functional MRI (BOLD fMRI) and diffusion tensor imaging (DTI) can now be applied to animal species as small as mice or songbirds. These techniques confirmed previous findings but are also beginning to reveal new phenomena that were difficult or impossible to study previously. These imaging techniques will lead to major technical and conceptual advances in systems neurosciences. We illustrate these new developments with studies of the song control and auditory systems in songbirds, a spatially organized neuronal circuitry that mediates ...
Source: Trends in Neurosciences - March 21, 2009 Category: Neuroscience Authors: Van der Linden A, Van Meir V, Boumans T, Poirier C, Balthazart J Tags: Trends Neurosci Source Type: journals

Friends and foes in synaptic transmission: the role of tomosyn in vesicle priming.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Priming is the process by which vesicles become available for fusion at nerve terminals and is modulated by numerous proteins and second messengers. One of the prominent members of this diverse family is tomosyn. Tomosyn has been identified as a syntaxin-binding protein; it inhibits vesicle priming, but its mode of action is not fully understood. The inhibitory activity of tomosyn depends on its N-terminal WD40-repeat domain and is regulated by the binding of its SNARE motif to syntaxin. Here, we describe new physiological information on the function of tomosyn and address possible interpretations of these results in t...
Source: Trends in Neurosciences - March 21, 2009 Category: Neuroscience Authors: Ashery U, Bielopolski N, Barak B, Yizhar O Tags: Trends Neurosci Source Type: journals

Calcium homeostasis, selective vulnerability and Parkinson's disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Parkinson's disease (PD) is a common neurodegenerative disorder of which the core motor symptoms are attributable to the degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Recent work has revealed that the engagement of L-type Ca(2+) channels during autonomous pacemaking renders SNc DA neurons susceptible to mitochondrial toxins used to create animal models of PD, indicating that homeostatic Ca(2+) stress could be a determinant of their selective vulnerability. This view is buttressed by the central role of mitochondria and the endoplasmic reticulum (linchpins of current theories about t...
Source: Trends in Neurosciences - March 21, 2009 Category: Neuroscience Authors: Chan CS, Gertler TS, Surmeier DJ Tags: Trends Neurosci Source Type: journals

Variability in the subcellular distribution of ion channels increases neuronal diversity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The exact location of an ion channel on the axo-somato-dendritic surface of a nerve cell crucially affects its functional impact. Recent high-resolution immunolocalization experiments examining the distribution of GABA and glutamate receptors, voltage-gated potassium and sodium channels and hyperpolarization-activated mixed cation (HCN) channels clearly demonstrate the lack of simple rules concerning their subcellular distribution. For example, the density of HCN1 subunits in pyramidal cells increases 60-fold from soma to distal dendrites but is uniform over the somato-dendritic surface of olfactory bulb external tufte...
Source: Trends in Neurosciences - March 17, 2009 Category: Neuroscience Authors: Nusser Z Tags: Trends Neurosci Source Type: journals

Hot flash: TRPV channels in the brain.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
TRPV1 (transient receptor potential, vanilloid) channels belong to a family of ligand-gated ion channels gated not only by the binding of certain lipophilic molecules but also by extracellular protons and physical stimuli such as heat or osmotic pressure changes. These nonselective cation channels are permeable to Na(+) and K(+) and are also very Ca(2+) permeable; in fact, TRPV1 is as Ca(2+) permeable as the NMDA receptor channel and can, thus, act as a trigger for Ca(2+)-mediated cell signaling. Although these channels are highly expressed in primary sensory afferents, accumulating evidence indicates that TRPV family ...
Source: Trends in Neurosciences - March 12, 2009 Category: Neuroscience Authors: Kauer JA, Gibson HE Tags: Trends Neurosci Source Type: journals