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 'Springer protocols feed by Neuroscience' source. Tue, 16 Mar 2010 18:17:38 +0100 http://www.medworm.com/index.php?rid=3287512&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-541-5_9 Glaucoma is a relatively common disease in which the pathological death of retinal ganglion cells causes progressive losses of sight, often leading to blindness. The diagnosis of glaucoma and the assessment of progression are based on a clinical quantification of the ocular characteristics of cupping of the optic nerve head, a loss of retinal nerve fiber layer thickness, and associated functional vision defects. Consequently, clinical tests are based on the quantification of these clinical characteristics of glaucomatous optic neuropathy. However, the basic neural and cellular pathophysiology that cause the characteristic signs of glaucoma cannot be studied in clinical patients and, therefore, animal models must be employed for basic research on glaucomatous optic neuropathy. For basic res... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3287512 Fri, 15 Jan 2010 00:00:00 +0100 3287512 http://www.medworm.com/index.php?rid=3287511&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-541-5_8 The generation and advancement of animal models have contributed significantly to the advancement of glaucoma research. This chapter describes and summarizes major nonprimate animal models useful for the study of this disease. Rodent models, both rats and mice, have been popular for glaucoma studies, because of the relatively better-developed genetic and genomic tools and the similarity of the relevant ocular structures between human and these animals. The larger animals, e.g., rabbit, feline, canine, bovine, ovine, and porcine models, have also been successfully used and provided valuable information on various aspects of the disease. Some of the models depicted in this chapter involve a transient or chronic ocular hypertension. Others do not affect intraocular pressure, but instead addre... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3287511 Fri, 15 Jan 2010 00:00:00 +0100 3287511 http://www.medworm.com/index.php?rid=3287510&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-541-5_7 Diabetic retinopathy threatens vision in millions of patients in the USA. Prolonged hyperglycemia causes irreversible pathological changes in the retina, leading to proliferative diabetic retinopathy with preretinal neovascularization and diabetic macular edema. Much of the disease progression appears similar between man and animal. Thus, animal models are essential in understanding the pathology of this disease and development of effective treatments. This chapter describes and discusses the use of the rat, mouse, and dog in diabetic retinopathy studies. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3287510 Fri, 15 Jan 2010 00:00:00 +0100 3287510 http://www.medworm.com/index.php?rid=3287509&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-541-5_6 Retinopathy of prematurity (ROP), a condition affecting premature infants, is characterized by pathological angiogenesis, or neovascularization (NV), of the retina. Much of what is known about the development of the retinal vasculature and the progression of ROP has been learned through the use of animal models of oxygen-induced retinopathy (OIR), which approximate the human condition. Animal models of OIR have provided a wealth of information regarding the cellular and molecular pathogenesis of ROP. Moreover, this information has contributed to a better understanding of other, nonocular, neovascular conditions. This chapter describes the various animal models of OIR, and explores their contributions to the understanding and treatment of ROP. (Source: Springer protocols feed by Neuroscienc... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3287509 Fri, 15 Jan 2010 00:00:00 +0100 3287509 http://www.medworm.com/index.php?rid=3287508&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-541-5_5 Age-related macular degeneration (AMD) has a number of characteristic features including late onset and accumulation of deposits (drusen) below the retinal pigment epithelium on Bruch’s membrane in the macula. A progressive increase in these deposits (in some individuals) leads to macular blindness, following either the local loss of the retinal pigment epithelium (geographic atrophy) or the hemorrhage of new blood vessels that originate in the choroid and invade the compartment between the photoreceptors and retinal pigment epithelium (choroidal neovascularization). Over the last few years a number of mouse models for AMD have been described that replicate some of the changes manifest in the human disease. This chapter begins with a description of the hallmarks of AMD, discusses som... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3287508 Fri, 15 Jan 2010 00:00:00 +0100 3287508 http://www.medworm.com/index.php?rid=3287507&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-541-5_4 Retinal degeneration is often used to describe a category of human eye diseases, which are characterized by photoreceptor loss leading to severe visual impairment and blindness. An important, yet heterogeneous group of such diseases is called Retinitis Pigmentosa (RP). To understand the molecular mechanisms of disease induction and progression and to develop therapeutical strategies for the preservation of vision in RP patients, appropriate animal models are used in many research laboratories worldwide. The largest category of models consists of mutant (spontaneous and genetically engineered) mice. However, in recent years, zebrafish has been established as a highly valuable tool for the study of various biological problems, including retinal degeneration. In this review, we summarize the ... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3287507 Fri, 15 Jan 2010 00:00:00 +0100 3287507 http://www.medworm.com/index.php?rid=3287506&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-541-5_3 Here we review both established and emerging approaches for studying retinal diseases. We primarily focus on the use of the mouse as a genetic model, as it is a mammalian model with many resources and is amenable to a variety of genetic manipulations. Additionally, we highlight two other organisms, zebrafish and fruit fly that are emerging as valuable genetic tools to study retinal disease. We discuss the ways in which near-complete genome sequences of these three organisms are revolutionizing our ability to investigate the complex mechanisms involved in retinal diseases. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3287506 Fri, 15 Jan 2010 00:00:00 +0100 3287506 http://www.medworm.com/index.php?rid=3287505&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-541-5_2 Because repairing visual dysfunction is the primary goal of therapy for retinal disease, a quantification of visual function is imperative for the evaluation of potential treatments for these diseases. The Visual Water Task and the Virtual Optokinetic System have been developed to conduct behavioral tests of vision in rodent models of retinal disease. These tests are less invasive and often more sensitive than physiological or anatomical measures of retinal function. Moreover, discrepancies between different measures of retinal function suggest that central and retinal adaptations may complicate the disease process. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3287505 Fri, 15 Jan 2010 00:00:00 +0100 3287505 http://www.medworm.com/index.php?rid=3287504&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-541-5_1 The conversion of wavelengths of light into information useful to the brain requires a tremendous degree of anatomic and functional specialization. The mammalian retina is a remarkably refined and adapted tissue that is capable of light detection, processing, and transmission of information to other sites in the central nervous system. In this chapter, we provide a brief overview of the anatomical features of the mammalian retina and discuss regional variability observed in the eyes of humans and other species. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3287504 Fri, 15 Jan 2010 00:00:00 +0100 3287504 http://www.medworm.com/index.php?rid=3287503&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-541-5_11 Retinal inflammatory disease of a putative autoimmune origin, known as autoimmune uveitis, affects 150,000 persons per year in the developed world and is a potentially blinding disease. The eye can be the only affected organ or uveitis can be part of a systemic syndrome. Animal models of uveitis induced by immunization with retinal antigens or through genetic engineering are used to study basic mechanisms, genetic control and therapeutic approaches. Although thymic expression of retinal antigens eliminates most autoreactive lymphocytes and positively selects natural regulatory T cells, peripheral tolerance to retina is inefficient due to the relative sequestration of retinal antigens. Therefore, residual autoreactive lymphocytes persist and can be activated by accidental encounter with sel... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3287503 Fri, 15 Jan 2010 00:00:00 +0100 3287503 http://www.medworm.com/index.php?rid=3287502&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-541-5_10 Ischemic disorders of the retina constitute a common cause of blindness and visual impairment worldwide. Retinal ischemia is a disorder initially caused by an imbalance between the supply of metabolic substrates to the retina and its demand for nutrients. If treatment cannot be implemented to correct this imbalance, the result is irreversible ischemic and apoptosis-related cascades leading to cell death. A number of animal models are available for both studying the mechanisms of retinal ischemia and exploring potential treatments to prevent neuronal degeneration. However, the vascular supply and induction procedures of retinal ischemia in animal models must be better understood for application to human disorders. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3287502 Fri, 15 Jan 2010 00:00:00 +0100 3287502 http://www.medworm.com/index.php?rid=3129190&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-529-3_9 Convection-enhanced drug delivery is a novel technology used to deliver drugs into brain tissue and which is currently evaluated in clinical trials. Drugs are delivered continuously via intracranial catheters and enable to achieve large volume of distributions at high drug concentrations with minimum systemic toxicity. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129190 Wed, 30 Dec 2009 16:15:51 +0100 3129190 http://www.medworm.com/index.php?rid=3129189&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-529-3_8 Recently, the nasal route for systemic drug delivery has gained great interest. It provides several advantages over other routes of drug administrations. These include rapid absorption, avoidance of the intestinal and hepatic presystemic disposition, and high potential for drug transfer to the cerebrospinal fluid. Unfortunately, the mucociliary clearance, which reduces the residence time of the nasally applied drugs, and the poor nasal permeability made it difficult for many drugs to be delivered through this route. Alternative approaches have been adopted to overcome these problems. These include the use of mucoadhesive formulations or chemical penetration enhancers. Vesicular drug delivery systems provide promising alternative for enhanced and controlled nasal drug delivery. (Source: Spr... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129189 Wed, 30 Dec 2009 16:15:51 +0100 3129189 http://www.medworm.com/index.php?rid=3129188&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-529-3_7 Intracarotid drug delivery was extensively investigated in the past; however, the approach was largely abandoned due to inconsistent benefits. Yet, intracarotid drug delivery is anecdotally used for treating a variety of brain diseases. The rapid advances in endovascular techniques now require a renewed evaluation of this therapeutic approach. This review describes the pharmacological principles, applications, and pitfalls of intraarterial drug delivery to brain tissue. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129188 Wed, 30 Dec 2009 16:15:50 +0100 3129188 http://www.medworm.com/index.php?rid=3129187&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-529-3_6 Direct central neural axis neuromodulation has become a viable means to treat chronic neurologic disease and injury. Although first described in 1898, technology has only recently allowed for strict modulation and adjustments of drug delivery into the centeral nervous system. Evolving congruently with understanding of the altered neurophysiology and an expanding pharmacologic armamentarium, intrathecal pump systems augment treatment in an ever expanding number of disorders. In this review, we present a general historical overview of direct neuroaxis delivery and discuss current indications for intrathecal delivery with considerations in patient and drug selection. Complications, both surgical and medical, are discussed in detail with focus on avoidance and management. (Source: Springer pro... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129187 Wed, 30 Dec 2009 16:15:50 +0100 3129187 http://www.medworm.com/index.php?rid=3129186&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-529-3_5 In the treatment of central nervous system diseases, therapeutic particles need to breach the blood–brain barrier (BBB) to reach their intended target, and it has long been known that this is a difficult barrier to breach. The barrier is both passive with tight junctions hindering passage of even rather small molecules, as well as active with transporters that can pump select molecules back into the bloodstream. The diseases include both those where this barrier has been compromised such as brain tumors, hemorrhagic stroke, and neurotrauma; as well as neurodegenerative disorders where the compromise is substantially less and often unnoticeable. In addition to the pharmaceutical solution which involves design of small molecules that may be administered orally or at least systemically,... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129186 Wed, 30 Dec 2009 16:15:50 +0100 3129186 http://www.medworm.com/index.php?rid=3129185&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-529-3_4 This chapter presents a mechanistic approach to in silico prediction of blood–brain barrier penetration by drugs and drug-like molecules. Focus is brought to critical analysis of experimental data used for modeling; several factors affecting data quality are discussed. The main experimental techniques used for measuring brain uptake are also briefly reviewed. The chapter provides a theoretical background for obtaining physicochemically reasonable and easily interpretable predictions of passive diffusion across blood–brain barrier, as well as some general advices regarding descriptor selection and model development. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129185 Wed, 30 Dec 2009 16:15:50 +0100 3129185 http://www.medworm.com/index.php?rid=3129184&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-529-3_3 A major challenge to drug delivery in the brain is caused by the blood–brain barrier (BBB), a composite of endothelial structures that exclude over 98% of small-molecule drugs and almost 100% of large-molecule neurotherapeutics from being transmitted to the brain. Current strategies for overcoming the BBB are either invasive, non-targeted, or demonstrating limited carrying capacity. Alternatively, non-invasive, transient, and local, image-guided blood–brain barrier disruption (BBBD) can be accomplished using focused ultrasound (FUS) exposure with intravascular injection of pre-formed microbubbles. Low-intensity FUS administered with microbubble-based ultrasound (US) contrast agents has been shown to transiently disrupt the BBB, allowing agents into the brain over several hours.... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129184 Wed, 30 Dec 2009 16:15:50 +0100 3129184 http://www.medworm.com/index.php?rid=3129183&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-529-3_2 Blood–brain barrier (BBB) limits drug delivery to the brain parenchyma. The ultimate goal of brain drug targeting technology is to deliver therapeutic agents across BBB. Insulin or transferrin as well as other endogenous peptides undergo receptor-mediated transcytosis or transport (RMT) across the BBB in vivo. Certain peptidomimetic monoclonal antibodies (mAb) for insulin receptor or transferrin receptor can also cross the BBB via RMT on the endogenous receptors. These mAb can act as molecular Trojan horses to shuttle into the brain a wide range of therapeutics including recombinant proteins, antibodies, RNA interference drugs, or non-viral gene products. During the last two decades, RMT-based brain drug transport techniques have been developed. This chapter will focus on introducing... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129183 Wed, 30 Dec 2009 16:15:50 +0100 3129183 http://www.medworm.com/index.php?rid=3129182&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-529-3_1 Limitation of drug delivery to the central nervous system (CNS) is a major problem in development of successful treatment of CNS disorders. Concepts of blood–brain barrier (BBB), its role in transport of various substances from the blood to the brain, as well as strategies to deliver drugs across the BBB have evolved over the past century. This chapter is an overview of the challenges and various approaches to drug delivery in CNS disorders as an introduction to other chapters, which deal with laboratory and clinical methods of CNS drug delivery. A classification of current strategies for drug delivery across the BBB is presented. These include novel formulations of drugs such as nanoparticles and strategies to cross the BBB. Drugs can be introduced directly into the CNS and various ... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129182 Wed, 30 Dec 2009 16:15:50 +0100 3129182 http://www.medworm.com/index.php?rid=3129181&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-529-3_15 Convection-enhanced delivery (CED) is a method of direct intracerebral parenchymal infusion. It has been previously studied as a mechanism of drug delivery in glioma therapy, which is the focus of this review, and much work has gone into the utilization of this technique. CED can be modeled using several equations that describe the transport of fluid into porous tissue. More practically, variability in CED catheters has been studied and catheters are currently being designed to optimize drug delivery. While CED is a theoretically excellent way to bypass the blood–brain barrier (BBB), limitations of current approaches include excessive backflow along the catheter tract and leakage into subarachnoid and intraventricular spaces. Several drugs, including many recombinant cytotoxins, have... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129181 Wed, 30 Dec 2009 16:15:50 +0100 3129181 http://www.medworm.com/index.php?rid=3129180&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-529-3_14 Virus-mediated gene therapies against brain tumors have been limited by the difficulty in tracking glioma cells infiltrating the brain parenchyma. Mesenchymal stem cells (MSCs) are particularly attractive cells for clinical use in cell-based therapies because they have tumor-targeting properties, can be easily isolated and expanded to the numbers required for use, and can be genetically manipulated with viral vectors. In addition, most of the replication-deficient adenoviral vectors that have been used to transduce MSCs are based on human Ad serotype 5 (Ad5). However, transduction of MSCs by conventional Ad5 vectors is inefficient, even when very high multiplicities of infection are used because MSCs do not express the cellular coxsackie-adenovirus receptor. This chapter describes in detai... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129180 Wed, 30 Dec 2009 16:15:50 +0100 3129180 http://www.medworm.com/index.php?rid=3129179&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-529-3_13 Gene therapy offers a novel approach for the treatment of experimental stroke. The adeno-associated virus (AAV) mediated vascular endothelial growth factor (VEGF) gene transfer into the ischemic brain is described in detail in this chapter. Other methods are also illustrated here, including the generation of mouse middle cerebral artery occlusion (MCAO) model, injection of viral vector into mouse brain, and standard assays for determining the successes of brain ischemia and gene transfer. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129179 Wed, 30 Dec 2009 16:15:50 +0100 3129179 http://www.medworm.com/index.php?rid=3129178&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-529-3_12 The blood–brain barrier (BBB), formed by the endothelial cells of the brain capillaries, restricts access to brain cells of blood-borne compounds and allows only nutrients essential for normal metabolism to reach brain cells. This results in the inability of both small and large therapeutic compounds to cross the BBB. Therefore, various strategies need to be developed to enhance the amount and concentration of therapeutic compounds in the brain. A new family of peptides called Angiopeps derived from proteins expressing the Kunitz domain is transported very efficiently across the BBB using a physiological mechanism. Angiopep-2 transport across the BBB is, in part, mediated by the low density lipoprotein receptor related protein 1 (LRP1). This peptide family is the base of the engineer... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129178 Wed, 30 Dec 2009 16:15:50 +0100 3129178 http://www.medworm.com/index.php?rid=3129177&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-529-3_11 Peptides have been shown to be potent regulators of central nervous system (CNS) activity. As such, peptide-based drugs can serve as a highly effective means to treat diseases of the CNS. Despite this potential, peptides have limited capacity to permeate across the blood–brain barrier (BBB). Nevertheless, advancing strategies in peptide drug design, delivery systems, and transporter targeting are emerging, with such potential to overcome the restrictive nature of the BBB. This chapter addresses peptide drug delivery into the CNS, and in vivo evaluation of peptide permeability across the BBB using the dual-artery in situ brain perfusion model coupled with the technique of capillary depletion. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129177 Wed, 30 Dec 2009 16:15:50 +0100 3129177 http://www.medworm.com/index.php?rid=3129176&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-529-3_10 Cellular transplantation is a promising therapeutic strategy for spinal cord injury (SCI); the clinical application of transplantation, however, will require safe and efficient protocols of cell delivery. Lumbar puncture (LP) is a minimally invasive delivery method that allows multiple cell deliveries into the intrathecal space, resulting in cell accumulation at the site of injury. Here we review the effectiveness of the LP technique in rodent models of SCI, the advantages of LP compared to traditional parenchymal injection and other minimally invasive methods, and provide detailed instructions for LP delivery of stem cells to the injured rat spinal cord. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129176 Wed, 30 Dec 2009 16:15:50 +0100 3129176 http://www.medworm.com/index.php?rid=3129200&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-474-6_7 Obsessive-compulsive disorder (OCD) inflicts uncontrollable, intrusive thoughts and ritualistic, compulsive behaviors affecting approximately 3% of the population. Clinical symptoms of OCD can be categorized as checking, hoarding, washing, or ordering. Mounting evidence suggests that OCD phenotypes can be modeled effectively, and with remarkable validity, through translational approaches in ethological animal models. Experimental models of OCD-like behavior, including nesting, marble burying, grooming, spatial alternation, and barbering allow researchers to investigate the neurobiological mechanisms responsible for this disorder. While its exact pathogenesis remains unknown, genetic factors also play a key role in OCD. Genetic animal models of OCD and related disorders are now becoming ava... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129200 Tue, 24 Nov 2009 00:00:00 +0100 3129200 http://www.medworm.com/index.php?rid=3129199&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-474-6_12 Schizophrenia is thought to be a polygenic disorder that is associated with considerable phenotypic heterogeneity across patients, including variations in age at onset, diagnostic symptoms and subsequent course of illness. Consequently, the generation of incisive mutant models for this disorder faces substantive challenges. The majority of mutant models for schizophrenia relate to putative pathobiological and pharmacological processes and to the functional roles of the increasingly large and diverse array of genes associated with risk for the disorder. The present review considers the application of mutant animal phenotypes to the study of pathobiological and pharmacological mechanisms thought to be relevant for schizophrenia, particularly in terms of dopaminergic and glutamatergic dysfunc... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129199 Tue, 24 Nov 2009 00:00:00 +0100 3129199 http://www.medworm.com/index.php?rid=3129198&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-474-6_11 Environmental enrichment studies of transgenic and mutant mouse models of brain disorders have facilitated exploration of gene × environment interactions and experience-dependent plasticity in response to enhanced mental and physical activity. Environmental enrichment was first shown to have beneficial effects in a transgenic mouse model of Huntington’s disease, followed by models of Alzheimer’s disease and other neurodegenerative disorders, as well as various neurodevelopmental and psychiatric disorders, including Rett syndrome and schizophrenia. Research involving mouse models of these various brain disorders has generally shown that environmental enrichment ameliorates brain dysfunction and associated behavioral signs, although the extent of beneficial effects may depe... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129198 Tue, 24 Nov 2009 00:00:00 +0100 3129198 http://www.medworm.com/index.php?rid=3129197&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-474-6_10 Depression, as part of a larger class of affective disorders, is one of the world’s most deleterious and widespread neurobehavioral diseases. However, much remains to be discovered concerning depression, due to the daunting complexity of its pathological mechanisms and etiology. Various animal models have been proposed over the years, some of which have come into widespread use, particularly in the area of pharmacological screening. By combining behavioral and physiological analyses with mutant and transgenic animal models, researchers are able to determine the role of specific genes and proteins in the pathogenesis of depression. Discussing several behavioral and transgenic/mutant rodent models, this chapter briefly summarizes the current progress in this area of psychiatric researc... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129197 Tue, 24 Nov 2009 00:00:00 +0100 3129197 http://www.medworm.com/index.php?rid=3129196&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-474-6_6 Estrogens are C-18 phenolic steroids derived from cholesterol and occur naturally in the forms of 17ß-estradiol, estrone, and estriol. Estrogen biosynthesis begins with the transfer of cystolic cholesterol from the cytoplasm into the mitochondrion of steroidogenic cells (1-3). This transfer of cholesterol into the mitochondrion is facilitated by the steroidogenic acute regulatory protein (StAR) (1). This is the rate-limiting step in androgen biosynthesis, as the cholesterol has to be transferred to the site where the cytochrome P450 side-chain cleavage enzyme (P450scc, CYP11A1) is located. As its name indicates, it catalyzes the cleavage of the side-chain of cholesterol (4) to form pregnenolone. Conversion of pregnenolone to estrogens involves five catalyzing enzymes which, in a numb... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129196 Tue, 24 Nov 2009 00:00:00 +0100 3129196 http://www.medworm.com/index.php?rid=3129195&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-474-6_5 Experimentally induced lesions of basal ganglia cause neurological anomalies such as hindlimb clasping and changes in motor activity, together with deficits in motor coordination and spatial learning. Some of these deficits have been described in mice genetically modified for Parkinson’s and Huntington’s disease. Symptoms, similar to those of neurological disorders, are found with lesions of dopaminergic neurons in murine models of Parkinson’s disease, including transgenic mice expressing mutant and wild-type SNCA encoding a-synuclein, Pitx3-deficient aphakia (ak) mice, and Park2 null mutants deficient in parkin. As with Huntington’s disease, HD transgenic and knock-in mice with variable CAG repeats have different onsets of anomalies and possess the same time-relate... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129195 Tue, 24 Nov 2009 00:00:00 +0100 3129195 http://www.medworm.com/index.php?rid=3129194&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-474-6_4 The inhibitory GABAA receptor plays important roles in the control of anxiety and sleep behavior. The a1 subunit-containing GABAA receptor is the major subtype, contributing to about 60% of all GABAA receptors in the brain. In this chapter, we present phenotypes observed in a GABAA receptor alpha-1 subunit (Gabra1) knockout line (KO). Our results are reviewed along with those from earlier publications on different Gabra1 mutant lines. We discovered a heightened anxiety profile in KO mice in several behavioral assays. Gabra1 KO mice were found to bury fewer marbles in a novelty-induced digging test, spent less time in the brightly lit area in the platform test, spent decreased time in the central area of the open field, and also had increased auditory startle responses. Increased anxiety be... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129194 Tue, 24 Nov 2009 00:00:00 +0100 3129194 http://www.medworm.com/index.php?rid=3129193&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-474-6_3 The two circling rat mutants described in this review illustrate how genetic animal models may serve to study multifaceted brain functions and dysfunctions. The LEW/Ztm-ci2/ci2 and BH.7A/Ztm-ci3/ci3 rat mutants both exhibit lateralized circling and hyperactivity and thus provide models for studying disturbances in cerebral asymmetry and their involvement in brain disorders. In both mutants, the abnormal lateralization appears to be a consequence of imbalances of nigrostriatal dopaminergic functions. Furthermore, most likely as a consequence of alterations in dopaminergic activity, both rat mutants exhibit maladaptive behavior in tests of emotionality. However, apart from circling, hyperactivity, and maladaptive behavior in response to external stimuli, the LEW/Ztm-ci2/ci2 and BH.7A/Ztm-ci3... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129193 Tue, 24 Nov 2009 00:00:00 +0100 3129193 http://www.medworm.com/index.php?rid=3129192&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-474-6_2 Rats have been extensively used to explore the brain mechanisms underlying psychiatric disorders. However, due to a lack of sufficient tools for the generation of knockout or mutant rats, there has been a general lag in the understanding of genetic factors in psychiatric and neurodevelopmental disorders, compared to other popular experimental animal models. Recently, several mutant and knockout rats have been generated using N-ethyl-N-nitrosourea (ENU)-driven target selected mutagenesis. Two of them, the serotonin transporter knockout (SERT-/-) rat and the dopamine D1 receptor mutant (DRD1-/-) rat, are described in relation to four important (neurodevelopmental) psychiatric disorders: depression, autism, schizophrenia and drug addiction. It has been shown that the SERT-/- rats display incr... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129192 Tue, 24 Nov 2009 00:00:00 +0100 3129192 http://www.medworm.com/index.php?rid=3129191&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-474-6_1 Zebrafish have traditionally been used as effective genetic and developmental models in biomedical research. Recently, the scope and utility of zebrafish in biomedical research has been further expanded with the implementation of new genetic techniques aimed at developing translational models of human pathogenesis. Additionally, screens measuring specific neurobehavioral and developmental phenotypes have proven to be very robust. This chapter further discusses the utility of zebrafish in biomedical research and highlights some of the genetic techniques used in the creation of transgenic and mutant strains. Behavioral phenotypes of genetically altered zebrafish are also discussed with respect to both their robust stress responses and similarity to human disorders. Specific emphasis is place... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3129191 Tue, 24 Nov 2009 00:00:00 +0100 3129191 http://www.medworm.com/index.php?rid=3100537&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-476-0_9 Calcium handling by mitochondria is important both because mitochondria can shape the cytosolic Ca2+ signals and because changes in mitochondrial Ca2+ concentration ([Ca2+]M) are important for controlling physiological functions such as respiration or programmed cell death. Accurate measurements of [Ca2+]M require selective location of the Ca2+ probe inside mitochondria and this is best achieved by targeting protein probes to the mitochondrial matrix. Aequorins are very adequate as Ca2+probes because: (1) they allow molecular engineering for targeting or for changing the Ca2+ affinity; (2) do not require irradiation for measurements; (3) Ca2+ buffering is small; (4) have a very steep Ca2+-dependence and a very wide dynamic range, which makes them ideal for detecting and quantifying Ca2+ mi... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3100537 Thu, 12 Nov 2009 00:00:00 +0100 3100537 http://www.medworm.com/index.php?rid=3100536&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-476-0_8 The endoplasmic reticulum (ER) is a complex and highly dynamic three-dimensional intracellular membranous system, which acts as a dynamic calcium store in the majority of eukaryotic cells. The special arrangement of intra-ER Ca2+ buffers, characterized by low affinity for Ca2+, in combination with SERCA pump activity keeps intraluminal Ca2+ ([Ca2+]L) at ~0.1–0.8 mM (Cell Calcium 38:303–310, 2005), thus creating a steep electrochemical gradient aimed at the cytosol. Activation of ER Ca2+ channels results in Ca2+ release, which contributes to [Ca2+]i elevation, whereas SERCA-dependent Ca2+ uptake assists termination of cytosolic Ca2+ signals. In addition, the continuous luminal space can act as a travelling route for free Ca2+ ions (“Ca2+ tunnels”), thus bypassing cyt... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3100536 Thu, 12 Nov 2009 00:00:00 +0100 3100536 http://www.medworm.com/index.php?rid=3100535&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-476-0_7 Neuronal Ca2+ signals occur in a very complex way. Direct imaging of Ca2+ changes in the soma, dendrites, and even single spines on fast time-scales greatly helps us understand the generation mechanism of diverse Ca2+ signaling events. However, Ca2+ imaging itself does not give information about the causal relationships between specific Ca2+ signals and specific functions. With the rapid improvements of new caged compounds, application or usage of uncaging/caging techniques has been expanded widely in biological research. Using caged compounds, the Ca2+ concentration in the target area can be either increased or lowered on a given time scale to various degrees. The most important advantage of the uncaging/caging technique is to control the intensity, duration, and area of light with high p... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3100535 Thu, 12 Nov 2009 00:00:00 +0100 3100535 http://www.medworm.com/index.php?rid=3100534&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-476-0_6 Ca2+-sensitive microelectrodes are time-consuming to make and require large robust cells. But, they do not add to buffering and do not require expensive equipment. I describe how to make and use the electrodes and briefly consider the leakage problem. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3100534 Thu, 12 Nov 2009 00:00:00 +0100 3100534 http://www.medworm.com/index.php?rid=3100533&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-476-0_5 Calcium indicators are widely used to monitor activity in living neuronal tissue because of the tight relation between action potential firing and increases in the intracellular calcium concentration. Here, we describe the use of genetically encoded calcium indicators (GECIs) of the latest generation for monitoring calcium levels in the mammalian brain. We discuss how to choose the sensor for a given experiment, how to introduce the sensor into the cells of interest and how to estimate the sensitivity of the sensor in situ and in vivo. Finally, we illustrate the application of these sensors for high resolution in vivo imaging of sensory-driven neuronal activity. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3100533 Thu, 12 Nov 2009 00:00:00 +0100 3100533 http://www.medworm.com/index.php?rid=3100532&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-476-0_4 In the last two decades, the study of Ca2+ homeostasis in living cells received a great impulse by the explosive development of genetically encoded Ca2+-indicators. The cloning of the Ca2+-sensitive photoprotein aequorin and of the green fluorescent protein (GFP) from the jellyfish Aequorea victoria has been enormously advantageous for the biologists. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3100532 Thu, 12 Nov 2009 00:00:00 +0100 3100532 http://www.medworm.com/index.php?rid=3100531&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-476-0_3 In this chapter, we review the theoretical and experimental foundations underling a quantitative approach to Ca2+ imaging, discuss equilibrium conditions and their violations and present a computational framework that can be used to estimate the spatial and temporal dynamics of Ca2+ signals based of fluorescence measurements with Ca2+ indicators. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3100531 Thu, 12 Nov 2009 00:00:00 +0100 3100531 http://www.medworm.com/index.php?rid=3100530&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-476-0_2 From an early start, more than two decades ago, Ca2+ measurements have evolved from the use of simple systems, built around an epifluorescent microscope, a fluorescent lamp and a photomultiplier, into highly complex set-ups exploiting solid-state light sources and Electron Multiplied cameras to capture in five dimensions with time resolutions from milliseconds to days. In addition to these technological advances, a series of conceptual breakthroughs have enabled microscopy to move well beyond the classical diffraction limit into the realm of optical nanoscopy. Further developments into miniaturization of optical components and advances in optical fibres are bringing Ca2+ imaging nearer to intra-vital microscopy applications. In this chapter, we review the basic hardware requirements for Ca... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3100530 Thu, 12 Nov 2009 00:00:00 +0100 3100530 http://www.medworm.com/index.php?rid=3100529&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-476-0_1 Calcium ions are the most ubiquitous and pluripotent signalling molecules, which regulate a wide array of physiological and pathological reactions. The specific system, controlling cellular Ca2+ homeostasis appeared very early in the evolution, being initially survival system preventing Ca2+-mediated cell damage. Subsequently, the steep Ca2+ gradients maintained by Ca2+ homeostatic molecular cascades became the basis for Ca2+ signalling. This signalling system utilises Ca2+ channels and transporters localised in plasmalemma and intracellular membranes to create highly organised and compartmentalised cytosolic Ca2+ fluctuations occurring within the spatial and temporal domains. Changes in cytosolic Ca2+ concentrations regulate a multitude of Ca2+-dependent proteins, which serve as “Ca... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3100529 Thu, 12 Nov 2009 00:00:00 +0100 3100529 http://www.medworm.com/index.php?rid=3100528&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-476-0_12 Glial cells are besides neurons the second major cell type of nervous systems and are either of neuroectodermal (macroglia) or mesodermal (microglia) origin. As electrically non-excitable cells, they employ calcium signals in response to most external stimuli, which initiate cellular activity. A variety of techniques are described here, which have been developed to monitor cellular calcium in different glial cell preparations from cell culture, acute tissue slices to in vivo measurements. New optical innovations in the last two decades, as e.g. generations of new calcium-sensitive fluorescent dyes, genetically-encoded calcium sensors and multiple applications of laser scanning microscopy have allowed novel experimental approaches and have provided important results for our understanding of... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3100528 Thu, 12 Nov 2009 00:00:00 +0100 3100528 http://www.medworm.com/index.php?rid=3100527&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-476-0_11 We describe the protocols for staining cells in newborn, juvenile, adult and aged tissue; discuss critical steps and possible pitfalls and introduce the multicolor imaging approach for functional characterization of specific cell types. We show, furthermore, that the use of MCBL can be extended to label other elements within the brain tissue as, for example, amyloid plaques in a mouse model of Alzheimer’s disease (AD). Finally, we illustrate the use of MCBL for two-photon calcium imaging of neurones and glia in the aged mouse cortex as well as the mouse cortex in an animal model of AD. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3100527 Thu, 12 Nov 2009 00:00:00 +0100 3100527 http://www.medworm.com/index.php?rid=3100526&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60761-476-0_10 The intracellular calcium concentration is one key parameter triggering numerous intracellular signalling pathways in neuronal cells. The development of optical techniques like fast confocal or 2-photon microscopy has made it possible to measure calcium dynamics even in sub-cellular compartments like dendrites and dendritic spines at high temporal and spatial resolution. This chapter provides experimental and technical details for different imaging techniques appropriate for calcium measurements in sub-cellular compartments, discusses specific advantages and limitations and calls attention to possible pitfalls. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=3100526 Thu, 12 Nov 2009 00:00:00 +0100 3100526 http://www.medworm.com/index.php?rid=2988893&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_4 Imaging of human brain function is possible only through a few techniques of which magnetic resonance is the safest and most widely used. The soft tissue contrast and high resolution functional maps of the human brain are making a profound contribution to our understanding of the brain function. Resolution and strength of activation signal in fMRI images depends on the static magnetic field. This fact must be fully exploited by availing the highest field fMRI scanners for neurofunctional studies. During the last decade of the last century, field strength of human imaging was raised to 8 T. As a result, today commercial 7-T MRI scanners are available for harnessing the strongest possible signal from the brain neuronal response to external stimulations. Such achievement has involved developm... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2988893 Fri, 01 May 2009 00:00:00 +0100 2988893 http://www.medworm.com/index.php?rid=2988892&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_2 This chapter discusses MRI hardware components, stimulus presentation devices, response, and physiological data collection systems. The general guidelines for MR-compatible hardware are also discussed. The chapter gives an overview of commonly used peripheral devices used in fMRI experiments, and it addresses the principles, performance aspects, and specifications of fMRI hardware. The target audience is quite broad and mathematical descriptions are kept to a minimum and qualitative descriptions are favored whenever possible. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2988892 Fri, 01 May 2009 00:00:00 +0100 2988892 http://www.medworm.com/index.php?rid=2988891&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_1 This chapter describes the basics of magnetic resonance imaging (MRI) and functional MRI (fMRI). It is aimed at beginners in the field and does not require any previous knowledge. Complex technical issues are made plausible by presenting plots and figures, rather than mathematical equations. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2988891 Fri, 01 May 2009 00:00:00 +0100 2988891 http://www.medworm.com/index.php?rid=2988890&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_15 The field of pain research has progressed immensely due to the advancement of brain imaging techniques. The initial goal of this research was to expand our understanding of the cerebral mechanisms underlying the perception of pain; more recently the research objectives have shifted toward chronic pain – understanding its origins, developing methods for its diagnosis, and exploring potential avenues for its treatment. While several different neuroimaging approaches have certain advantages for the study of pain, fMRI has ultimately become the most widely utilized imaging technique over the past decade because of its noninvasive nature, high-temporal and spatial resolution, and general availability; thus, the following chapter will focus on fMRI and the special aspects of this technique... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2988890 Fri, 01 May 2009 00:00:00 +0100 2988890 http://www.medworm.com/index.php?rid=2778249&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_3 In this chapter, we discuss technical considerations regarding pulse sequence selection and sequence parameter selection that can affect fMRI studies. The major focus is on optimizing MRI data acquisitions for blood oxygen level-dependent signal detection. Specific recommendations are made for generic 1.5-T and 3.0-T MRI scanners. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778249 Thu, 30 Apr 2009 23:00:00 +0100 2778249 http://www.medworm.com/index.php?rid=2778248&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_7 fMRI is a powerful tool used in the study of brain function. It can non-invasively detect signal changes in areas of the brain where neuronal activity is varying. This chapter is a comprehensive description of the various steps in the statistical analysis of fMRI data. This will cover topics such as the general linear model (including orthogonality, haemodynamic variability, noise modelling, and the use of contrasts), multi-subject statistics, and statistical thresholding (including random field theory and permutation methods). (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778248 Thu, 30 Apr 2009 23:00:00 +0100 2778248 http://www.medworm.com/index.php?rid=2778247&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_6 This chapter describes the procedures applied to fMRI data prior to their statistical analysis. This usually begins with converting the data from original MR format to a form that can be used by the analysis software. The data are then motion corrected. If an anatomical scan is collected for the subject, then it would be co-registered with the fMRI, and may serve to estimate the warps needed to spatially normalise the fMRI to some standard space. The final pre-processing step is usually to smooth the data. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778247 Thu, 30 Apr 2009 23:00:00 +0100 2778247 http://www.medworm.com/index.php?rid=2778246&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_5 This chapter addresses issues particular to the optimal design of fMRI experiments. It describes procedures for isolating the psychological process of interest and gives an overview of block, event-related, and participant-response dependent designs. An additional focus is placed on data analysis with emphasis on optimizing and isolating the neuroimaging signal in activated brain regions. Finally, the chapter addresses a number of practical matters including optimal sample sizes and trial durations that confront all researchers when designing their experiments. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778246 Thu, 30 Apr 2009 23:00:00 +0100 2778246 http://www.medworm.com/index.php?rid=2778245&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_8 This chapter is about modelling-distributed brain responses and, in particular, the functional integration among neuronal systems. Inferences about the functional organisation of the brain rest on models of how measurements of evoked responses are caused. These models can be quite diverse, ranging from conceptual models of functional anatomy to mathematical models of neuronal and haemodynamics. The aim of this chapter is to introduce dynamic causal models. These models can be regarded as generalisations of the simple models employed in conventional analyses of regionally specific brain responses. In what follows, we will start with anatomical models of functional brain architectures, which motivate some of the basic principles of neuroimaging. We then review briefly statistical models (e.g... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778245 Thu, 30 Apr 2009 23:00:00 +0100 2778245 http://www.medworm.com/index.php?rid=2778244&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_9 We describe how brain atlases, and the computational tools that align new datasets with them, facilitate comparison of brain data across experiments, laboratories, and from different imaging devices. The major philosophies are presented that underlie the construction of probabilistic atlases, which store information on anatomic and functional variability in a population. Algorithms that create composite brain maps and atlases based on multiple subjects are examined. We show that group patterns of cortical organization, asymmetry, and disease-specific trends can be resolved that may not be apparent in individual brain maps. Finally, we describe the development of four-dimensional maps that store information on the dynamics of brain change in development and disease. (Source: Springer protoc... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778244 Thu, 30 Apr 2009 23:00:00 +0100 2778244 http://www.medworm.com/index.php?rid=2778243&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_10 Neuroimaging has, in many respects, revolutionized the study of cognitive neuroscience, the discipline that attempts to determine the neural mechanisms underlying cognitive processes. Early studies of brain–behavior relationships relied on a precise neurological exam as the basis for hypothesizing the site of brain damage that was responsible for a given behavioral syndrome. The advent of structural brain imaging, first with computerized tomography and later with magnetic resonance imaging, paved the way for more precise anatomical localization of the cognitive deficits that manifest after brain injury. In recent years, functional neuroimaging, broadly defined as techniques that provide measures of brain activity, has further increased our ability to study the neural basis of behavio... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778243 Thu, 30 Apr 2009 23:00:00 +0100 2778243 http://www.medworm.com/index.php?rid=2778242&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_12 Selective attention is an essential cognitive ability that permits us to effectively process and act upon relevant information while ignoring distracting events. The human capacity to focus attention is at the core of mental functioning. Elucidating the neural bases of human selective attention remains a key challenge for neuroscience and represents an essential aim in translational efforts to ameliorate attentional deficits in a wide variety of neurological and psychiatric disorders. In this chapter, we discuss how functional imaging methods have helped us to understand fundamental aspects of attention: How attention is controlled, and how this control results in the selection of relevant stimuli. Work from our group and from others will be discussed. We will focus on fMRI methods, but wh... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778242 Thu, 30 Apr 2009 23:00:00 +0100 2778242 http://www.medworm.com/index.php?rid=2778241&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_11 Language refers to the uniquely human capacity for communication through productive combination of symbolic representations. Functional neuroimaging studies have in recent decades greatly expanded our knowledge of the brain systems supporting language, producing a dramatic reawakening of interest in this topic and a call to revise and extend the nineteenth century neuroanatomical model formulated by Broca, Wernicke, and others. This chapter presents some theoretical issues regarding functional imaging of language systems, a model of the functional neuroanatomy of language based on recent empirical results in several selected processing domains, and a survey of language mapping paradigms in common clinical use. A central theme is that interpretation of fMRI language studies depends on an in... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778241 Thu, 30 Apr 2009 23:00:00 +0100 2778241 http://www.medworm.com/index.php?rid=2778240&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_13 Numerous fMRI studies have investigated the network of brain regions critical for memory. Whereas neuropsychological techniques can delineate the brain regions that are necessary for intact memory function, neuroimaging techniques can be used to investigate which regions are recruited during healthy memory formation, storage, and retrieval. For example, fMRI studies have shown that lateral prefrontal cortex (PFC) supports some components of working memory function. However, working memory is not localized to a single brain region but is likely a property of the functional interaction between the PFC and posterior brain regions. The medial temporal lobe (MTL) and its connections with neocortical, prefrontal, and limbic structures are implicated in episodic memory. Semantic memory is mediate... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778240 Thu, 30 Apr 2009 23:00:00 +0100 2778240 http://www.medworm.com/index.php?rid=2778239&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_14 Recent brain imaging work has expanded our understanding of the mechanisms of perceptual, cognitive, and motor functions in human subjects, but research into the cerebral control of emotional and motivational function is at a much earlier stage. Important concepts and theories of emotion are briefly introduced, as are research designs and multimodal approaches to answering the central questions in the field. We provide a detailed inspection of the methodological and technical challenges in assessing the cerebral correlates of emotional activation, perception, learning, memory, and emotional regulation behavior in healthy humans. fMRI is particularly challenging in structures such as the amygdala as it is affected by susceptibility-related signal loss, image distortion, physiological and mo... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778239 Thu, 30 Apr 2009 23:00:00 +0100 2778239 http://www.medworm.com/index.php?rid=2778238&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_15 The field of pain research has progressed immensely due to the advancement of brain imaging techniques. The initial goal of this research was to expand our understanding of the cerebral mechanisms underlying the perception of pain; more recently the research objectives have shifted toward chronic pain – understanding its origins, developing methods for its diagnosis, and exploring potential avenues for its treatment. While several different neuroimaging approaches have certain advantages for the study of pain, fMRI has ultimately become the most widely utilized imaging technique over the past decade because of its noninvasive nature, high-temporal and spatial resolution, and general availability; thus, the following chapter will focus on fMRI and the special aspects of this technique... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778238 Thu, 30 Apr 2009 23:00:00 +0100 2778238 http://www.medworm.com/index.php?rid=2778237&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_16 The extensive application of fMRI to the assessment of the human sensorimotor system has disclosed a complexity that is largely beyond our original understanding. From the available data, it is accepted that this system consists of a large, and somewhat yet unknown, number of cortical and subcortical areas, with a precise location and a specialized function. In particular, a large number of regions in the frontal and parietal lobes contribute to different aspects of motor act performance. It is also evident that the properties and potentialities of this network still need to be fully elucidated by further research. Defining how the human sensorimotor system works is of outmost importance for understanding its dysfunction in case of diseases and also to develop potential therapeutic strateg... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778237 Thu, 30 Apr 2009 23:00:00 +0100 2778237 http://www.medworm.com/index.php?rid=2778236&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_17 The human visual system consists of a large, yet unknown number of cortical areas. We summarize the efforts made to identify these areas, using the macaque visual cortex as a guide. So far, retinotopic mapping has identified several regions and study of functional properties such as motion and shape has revealed further expanses of visual cortex. Macaques and humans share early areas (V1, V2, and V3) and a motion-sensitive middle temporal (MT/V5) region, but the intervening cortex has considerably developed in humans with the appearance of new areas. The kinetic occipital region is located in this part of cortex between V3A and the human MT/V5 complex. Several regions sensitive to motion and even higher order motion have been described in parietal cortex. On the other hand, both dorsal and... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778236 Thu, 30 Apr 2009 23:00:00 +0100 2778236 http://www.medworm.com/index.php?rid=2778235&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_18 Over the years, blood oxygen level-dependent (BOLD) fMRI has made important contributions to the understanding of central auditory processing in humans. Although there are significant technical challenges to overcome in the case of auditory fMRI, the unique methodological advantage of fMRI as an indicator of population neural activity lies in its spatial precision. It can be used to examine the neural basis of auditory representation at a number of spatial scales, from the micro-anatomical scale of population assemblies to the macro-anatomical scale of cortico-cortical circuits. The spatial resolution of fMRI is maximised in the case of mapping individual brain activity, and here it has been possible to demonstrate known organisational features of the auditory system that have hitherto bee... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778235 Thu, 30 Apr 2009 23:00:00 +0100 2778235 http://www.medworm.com/index.php?rid=2778234&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_19 The variable effectiveness of reparative and recovery mechanisms following tissue damage is among the factors that might contribute to explain, at least partially, the paucity of the correlation between clinical and magnetic resonance imaging (MRI) findings in patients with white matter disorders. Among the mechanisms of recovery, brain plasticity is likely to be one of the most important with several possible different substrates (including increased axonal expression of sodium channels, synaptic changes, increased recruitment of parallel existing pathways or “latent” connections, and reorganization of distant sites). The application of fMRI has shown that plastic cortical changes do occur after white matter injury of different aetiology, that such changes are related to the e... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778234 Thu, 30 Apr 2009 23:00:00 +0100 2778234 http://www.medworm.com/index.php?rid=2778233&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_20 Stroke is a major cause of long-term disability worldwide. One of the key factors underpinning recovery of function is reorganization of surviving neural networks. Noninvasive techniques such as fMRI allow this reorganization to be studied in humans. However, the design of experiments involving patients with impairment requires careful consideration and is often constrained. Difficulty with some tasks can lead to a number of performance confounds, and so tasks and task parameters that avoid or minimize this should be selected. Furthermore, when studying patients with cerebrovascular disease, it is important to consider the possibility that the blood oxygen level dependent signal may be altered and affect interpretation of results. Despite these potential problems, careful experimental desi... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778233 Thu, 30 Apr 2009 23:00:00 +0100 2778233 http://www.medworm.com/index.php?rid=2778232&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_21 Functional neuroimaging has become an important tool for clinical research, with the potentiality to provide information on psychiatric disease pathology and treatment response. We review functional magnetic resonance imaging (fMRI) research findings for six psychiatric disorders: schizophrenia, major depressive disorder, bipolar disorder, obsessive-compulsive disorder, posttraumatic stress disorder, and Alzheimer’s disease. Brain functional abnormalities and possible underlying mechanisms for disease symptoms are discussed, with a focus on future clinical implications for fMRI in psychiatric disease. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778232 Thu, 30 Apr 2009 23:00:00 +0100 2778232 http://www.medworm.com/index.php?rid=2778231&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_23 This chapter provides an overview of the application of functional MRI applied to the field of Epilepsy and is divided into two sections, covering cognitive mapping and imaging of paroxysmal activity, respectively. In addition to a review of the most scientifically and clinically relevant findings, technical and methodological background information is provided to help the reader better understand the data acquisition process. We show how both approaches may play a role in the pre-surgical evaluation of patients with drug-resistant focal epilepsy and provide opportunities for new insights into the neuropathological processes that underlie both focal and generalised epilepsy. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778231 Thu, 30 Apr 2009 23:00:00 +0100 2778231 http://www.medworm.com/index.php?rid=2778230&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_22 fMRI is a technology with great promise as a tool to probe abnormalities of brain activity in neurodegenerative diseases. The detection of functional brain abnormalities may be useful, in the appropriate clinical context, for early diagnosis, differential diagnosis, or prognostication. Prediction of response to treatment or therapeutic monitoring may also be possible with fMRI. In addition, fMRI has the potential to provide a variety of scientific insights that may have clinical relevance, including compensatory hyperactivation of brain circuits or genetic modulation of functional brain activity. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778230 Thu, 30 Apr 2009 23:00:00 +0100 2778230 http://www.medworm.com/index.php?rid=2778229&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_24 Functional magnetic resonance imaging has evolved from a basic research application to a useful clinical tool that also has found its place in modern neurosurgery. The localization of functional important brain areas as language and sensorimotor cortex has been the focus of numerous investigations and can now be implemented in neurosurgical planning. Since the neurosurgeon must have detailed knowledge about the individual anatomy and related neurological function to resect a brain tumor with the highest safety, the need for individualized maps of brain function is essential. Advanced fMRI techniques and modern imaging methods contribute significantly to brain mapping as do already established concepts of electrophysiological monitoring and the Wada test. The implementation of functional ma... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778229 Thu, 30 Apr 2009 23:00:00 +0100 2778229 http://www.medworm.com/index.php?rid=2778228&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_25 Modern drug development presents new challenges by the unmet medical needs of chronic neurological and psychiatric disease. Imaging provides a potentially powerful tool for more efficiently translating pre-clinical and clinical studies and enhancing confidence in progression through early phase clinical development. Pharmacological MRI (phMRI) refers specifically to the applications of fMRI methods for direct or indirect measures of drug action. phMRI can be coupled to advanced structural methods to relate pharmacological effects and functional anatomy. Current and potential applications of phMRI to target stratification, patient validation, and pharmacodynamic studies are described. While great new opportunities could arise from extension of these methods as surrogate markers of clinical ... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778228 Thu, 30 Apr 2009 23:00:00 +0100 2778228 http://www.medworm.com/index.php?rid=2778227&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_26 Motor deficits contribute to disability in a number of neurological conditions. A wide range of emerging restorative therapies has the potential to reduce this by favorably modifying function. In many medical contexts, a study of target organ function improves efficacy of a therapeutic intervention. However, the optimal methods to prescribe a restorative therapy in the setting of central nervous system (CNS) disease are not clear. Brain mapping studies have the potential to provide useful insights in this regard. Examples of restorative therapies are provided, and human trials are summarized whereby brain mapping data have proven useful in promoting motor improvements in subjects with a neurological condition. In some cases, brain mapping findings that correlate with better outcome with sp... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778227 Thu, 30 Apr 2009 23:00:00 +0100 2778227 http://www.medworm.com/index.php?rid=2778226&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_27 Recent years have seen a renewed interest in brain anatomy in the neuroimaging community. Developments in techniques for structural MR acquisition and analysis have opened new opportunities for structural mapping of the living human brain. For example, high-resolution MR imaging can be used for “in vivo histology”, techniques such as voxel-based morphometry can be used to localise structural variation across populations, diffusion imaging provides information on system-level anatomical connectivity. fMRI studies are increasingly making use of the information provided by such structural mapping techniques in order to discover the anatomical substrate for observed functional effects. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778226 Thu, 30 Apr 2009 23:00:00 +0100 2778226 http://www.medworm.com/index.php?rid=2778225&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-919-2_28 Evidence to date shows that fMRI of the spinal cord (spinal fMRI) can reliably demonstrate regions involved with sensation of tactile, thermal, and painful stimuli, and with motor tasks. The spin-echo-based spinal fMRI method with “signal enhancement by extravascular protons” contrast has been developed more extensively than the BOLD (blood oxygen level dependent)-based method. Results have demonstrated good localization to areas of activity within the spinal cord cross-section and to the spinal cord segmental level, in both the cervical and lumbar spinal cord, with a range of thermal stimuli as well as tactile, vibration, and motor stimuli. The method has also demonstrated the first results in the injured spinal cord with thermal and motor stimuli, and in people with multiple ... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2778225 Thu, 30 Apr 2009 23:00:00 +0100 2778225 http://www.medworm.com/index.php?rid=2508362&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-263-6_9 This is perhaps the most beautiful time in human history; it is really pregnant with all kinds of creative possibilities made possible by science and technology.  Jonas Salk’s quotation seems particularly pertinent to recent developments in imaging technology, which have provided both beauty and insight in equal measure. We can now manipulate biological systems, both genetically and otherwise, to introduce fluorescent markers, literally adding colour to our preparations. These advances have occurred in parallel with remarkable developments in microscopy technology, with novel means of illumination and light detection allowing imaging to be done in ever more inaccessible places, with ever improving temporal and spatial resolution. A critical step in the application of these new... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2508362 Sat, 01 Nov 2008 00:00:00 +0100 2508362 http://www.medworm.com/index.php?rid=2508361&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-263-6_8 Throughout our nervous system, excitation and inhibition are exquisitely balanced to enable a multitude of functions. When this balance is disrupted, neurons experience a surplus or a deficit in excitation, either of which can have devastating consequences. In the cortex, excitation and inhibition are mediated by glutamatergic pyramidal cells and GABAergic interneurons, respectively. The loss of GABAergic inhibition in the epileptic brain places neurons in a hyperexcitable state in which they are vulnerable to the high-frequency firing that defines seizures. The association between seizures and a loss of GABAergic transmission is supported by numerous investigations of epileptic patients and animal models of epilepsy(1–3). For example, brain tissue from patients suffering from mesial... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2508361 Sat, 01 Nov 2008 00:00:00 +0100 2508361 http://www.medworm.com/index.php?rid=2508360&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-263-6_7 Benign familial neonatal convulsions (BFNC) is caused by mutations in the KCNQ2 (Kv7.2) or KCNQ3 (Kv7.3) genes. These genes encode the KCNQ2 and KCNQ3 subunits that comprise the neuronal M-type potassium channel (M channel). While numerous studies have provided evidence for the inhibitory role of normally functioning M channels in key brain structures related to seizures and epileptogenesis, the BFNC sequelae from mutation to seizure and ultimately to remission is likely very complex. In an effort to determine the role of the KCNQ genes in epilepsy, a number of mouse models with either spontaneous or transgenic mutations or targeted deletions in the Kcnq2 or Kcnq3 gene have been described. We discuss seminal findings from the Kcnq2 knockout, the dominant-negative Kcnq2 G279S, the Sz... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2508360 Sat, 01 Nov 2008 00:00:00 +0100 2508360 http://www.medworm.com/index.php?rid=2508359&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-263-6_6 Many experimental studies of epilepsy are based on rodent models induced by chemical or electrical insult as an instigator of seizures. Although such studies are useful in observing the physiological events that may occur during epileptogenesis, the great complexity of changes that ensue between first seizure and epilepsy makes it difficult to ascribe cause-and-effect to any single protein. In contrast, spontaneous mutations or mutations using gene targeting in mice provide a unique opportunity to evaluate a single protein, at cellular to whole organism level, for its role in epilepsy. Such approaches have uncovered a number of genes, some expected and others unexpected, which may provide novel targets for further study and drug design. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2508359 Sat, 01 Nov 2008 00:00:00 +0100 2508359 http://www.medworm.com/index.php?rid=2508358&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-263-6_5 Tuberous sclerosis complex (TSC) is a very important cause of epilepsy particularly in children. Seizures are seen in up to 90% of patients with TSC and often very resistant to standard medical therapies. In addition, patients with TSC also frequently suffer from autism as well as mental retardation and various psychiatric disorders. The causative TSC1 and TSC2 genes were identified in the 1990s. Despite tremendous growth in our knowledge of the TSC genes, encoded proteins, and participation in signaling pathways, we have not yet developed breakthrough therapies that will significantly improve the quality of life of these patients. While such advances are clearly very difficult endeavors, the relative lack of appropriate animal models has impeded such translational research. Recent develop... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2508358 Sat, 01 Nov 2008 00:00:00 +0100 2508358 http://www.medworm.com/index.php?rid=2508357&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-263-6_4 For many years, scientists have developed animal models of epilepsy to study specific aspects of the human condition. Rodents are the species of choice in the vast majority of these studies. In a departure from these rodent-centric models, we here describe zebrafish (Danio rerio), a genetically tractable vertebrate that is particularly well suited to epilepsy research. Zebrafish do not possess the complex central nervous system we have come to expect in other animal models and will never be mistaken for miniature versions of the complex mammalian brain. Nonetheless, the nervous system of this “simple” vertebrate is comprised of individual elements (glutamatergic excitatory neurons and GABAergic inhibitory neurons, for example) that we routinely study as critical to the generati... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2508357 Sat, 01 Nov 2008 00:00:00 +0100 2508357 http://www.medworm.com/index.php?rid=2508356&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-263-6_3 Here we describe a novel model system based on the transparent albino Xenopus laevis tadpole which is particularly well suited for the study of seizures and their sequelae within the intact developing brain. This system allows in vivo imaging of neuronal circuit activity with single-cell resolution, as well as acute and long-term imaging of neuronal growth and synapse formation, within the intact unanesthetized brain. Mounting evidence supports a strong role for neuronal transmission in regulating major aspects of brain circuit formation, including synaptogenesis, synapse strengthening and elimination, as well as axonal and dendritic arbor growth. Given the high incidence of seizures during periods of early brain development in humans, such model systems are necessary to better understand ... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2508356 Sat, 01 Nov 2008 00:00:00 +0100 2508356 http://www.medworm.com/index.php?rid=2508355&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-263-6_2 There has been an increased interest recently in various Drosophila models of human disease. The goals are to uncover the fundamental biological principles underlying causes and cures of human pathology utilizing the power of Drosophila genetics. A particularly exciting prospect is that new therapeutics could be forthcoming through identification of disease-causing genes followed by targeted drug development or by the development of platforms for high-throughput drug screening. This chapter reviews a model of human epilepsy based on a set of seizure-sensitive Drosophila mutants that exhibit features resembling some human epilepsies. Especially interesting are descriptions of a novel class of mutations that are second-site seizure-suppressor mutations. These mutations revert epilepsy phenot... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2508355 Sat, 01 Nov 2008 00:00:00 +0100 2508355 http://www.medworm.com/index.php?rid=2508354&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-263-6_1 Acquiring a holistic understanding of epilepsy, an intricate and often multifactorial disorder, is certain to necessitate considerable effort from a diverse and global assortment of scientists and clinicians. For most of its history, a combination of basic research with rodent models and clinical research with patients has dominated the approach of the epilepsy research community. These complementary approaches will undoubtedly remain as the ultimate direction in which research should move before new treatments for epilepsy are established, as mammalian nervous systems are exemplified by a degree of complexity, which sets them apart from those of invertebrates. Nonetheless, epilepsy researchers are inundated with inexplicable genetic, anatomical, and physiological defects, which underlie t... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2508354 Sat, 01 Nov 2008 00:00:00 +0100 2508354 http://www.medworm.com/index.php?rid=2508353&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-263-6_14 Neurogenesis persists in the adult mammalian hippocampal dentate gyrus and is influenced by epileptogenic insults. Studies of rodent mesial temporal lobe epilepsy (mTLE) models indicate that status epilepticus acutely increases dentate granule cell (DGC) neurogenesis, but in chronic stages neurogenesis may decrease. The functional implications of altered neurogenesis in either stage of mTLE are poorly understood. Accumulating evidence suggests, however, that altered neurogenesis contributes to several well-characterized cellular abnormalities seen in human and experimental mTLE. These abnormalities include mossy fiber sprouting, DGC layer dispersion, aberrant migration of DGC progenitors, and the appearance of DGCs in ectopic locations or with hilar basal dendrites. The mechanisms underlyi... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2508353 Sat, 01 Nov 2008 00:00:00 +0100 2508353 http://www.medworm.com/index.php?rid=2508352&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-263-6_13 Theoretically, gene therapy offers an attractive alternative for the treatment of focal epilepsies, and recently, studies have established the basic viability of anti-seizure gene therapy by employing a number of diverse approaches. Using recombinant adeno-associated virus (AAV) vectors, significant seizure suppression has been obtained in vivo by interrupting NMDA receptor function or by altering GABA receptor composition. Similarly, engineering cells to release GABA or adenosine has been shown to exert significant anti-seizure actions. In addition, studies have reported seizure suppression using in vivo, viral vector-mediated expression of GDNF, ICP10PK , or clostridial light chain. At present though, studies with the neuroactive peptides, galanin and neuropeptide Y (NPY), have pro... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2508352 Sat, 01 Nov 2008 00:00:00 +0100 2508352 http://www.medworm.com/index.php?rid=2508351&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-263-6_12 Understanding seizure generation, the transition from interictal to ictal states, and its underlying mechanisms requires continuous electrophysiologic monitoring. Though the duration of monitoring may vary from brief experiments over minutes to months of continuous recording, all recording of this nature requires a similar set of hardware and software tools. This chapter reviews the basic setup and requirements for successful continuous EEG monitoring in vivo and provides a set of computational “tools” that our group has found useful for continuous EEG monitoring in the laboratory. These include methods for seizure detection and basic analysis. References are provided for approaches used by groups involved in this kind of recording in animal models of epilepsy and humans. While... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2508351 Sat, 01 Nov 2008 00:00:00 +0100 2508351 http://www.medworm.com/index.php?rid=2508350&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-263-6_11 Organotypic hippocampal slice cultures experience trauma, deafferentation due to cell loss or transection of afferent pathways, and neuronal circuitry rearrangements much like the events that can lead to acquired temporal lobe epilepsy. Organotypic hippocampal slice cultures can be maintained for months in vitro and exhibit a latent period followed by onset of electrographic seizures involving the dentate granule cells, which is a hallmark of epileptogenesis and acquired epilepsy in humans and in vivo animal models. The advantages of organotypic hippocampal slice cultures over in vivo models are that slice cultures exhibit a relatively short latent period and can be treated quickly and easily with a known concentration of reagent without unwanted systemic side effects. They are also more a... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2508350 Sat, 01 Nov 2008 00:00:00 +0100 2508350 http://www.medworm.com/index.php?rid=2508349&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-263-6_10 In the epilepsy field, the creation of large-scale data-driven models that incorporate decades worth of experimental data has led to substantial innovations over current methodologies. Such models and sophisticated visualization software that makes the models truly come to life have brought computational neuroscience closer to reality for all epilepsy researchers. In this chapter, we discuss detailed, data-driven models that have resulted in significant, testable, theoretical advances that have contributed to our knowledge of how large-scale biological neuronal networks interact to promote hyperexcitability and hypersynchrony in epilepsy syndromes. Additionally we elaborate on how computational advances in software infrastructure have greatly increased the accessibility and applicability o... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2508349 Sat, 01 Nov 2008 00:00:00 +0100 2508349 http://www.medworm.com/index.php?rid=2364572&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_9 Data integration is particularly difficult in neuroscience; we must organize vast amounts of data around only a few fragmentary functional hypotheses. It has often been noted that computer simulation, by providing explicit hypotheses for a particular system and bridging across different levels of organization, can provide an organizational focus, which can be leveraged to form substantive hypotheses. Simulations lend meaning to data and can be updated and adapted as further data come in. The use of simulation in this context suggests the need for simulator adjuncts to manage and evaluate data. We have developed a neural query system (NQS) within the NEURON simulator, providing a relational database system, a query function, and basic data-mining tools. NQS is used within the simulation con... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2364572 Thu, 29 Nov 2007 05:00:00 +0100 2364572 http://www.medworm.com/index.php?rid=2364571&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_8 A key challenge for neuroinformatics is to devise methods for representing, accessing, and integrating vast amounts of diverse and complex data. A useful approach to represent and integrate complex data sets is to develop mathematical models [Arbib (The Handbook of Brain Theory and Neural Networks, pp. 741–745, 2003); Arbib and Grethe (Computing the Brain: A Guide to Neuroinformatics, 2001); Ascoli (Computational Neuroanatomy: Principles and Methods, 2002); Bower and Bolouri (Computational Modeling of Genetic and Biochemical Networks, 2001); Hines et al. (J. Comput. Neurosci. 17, 7–11, 2004); Shepherd et al. (Trends Neurosci. 21, 460–468, 1998); Sivakumaran et al. (Bioinformatics 19, 408–415, 2003); Smolen et al. (Neuron 26, 567&ndash... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2364571 Thu, 29 Nov 2007 05:00:00 +0100 2364571 http://www.medworm.com/index.php?rid=2364570&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_6 One of the more important recent additions to the NEURON simulation environment is a tool called ModelView, which simplifies the task of understanding exactly what biological attributes are represented in a computational model. Here, we illustrate how ModelView contributes to the understanding of models and discuss its utility as a neuroinformatics tool for analyzing models in online databases and as a means for facilitating interoperability among simulators in computational neuroscience. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2364570 Thu, 29 Nov 2007 05:00:00 +0100 2364570 http://www.medworm.com/index.php?rid=2364569&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_19 The Alzheimer Research Forum Web site ( http://www.alzforum.org ) is an independent research project to develop an online community resource to manage scientific knowledge, information, and data about Alzheimer disease (AD). Its goals are to promote rapid communication, research efficiency, and collaborative, multidisciplinary interactions. Introducing new knowledge management approaches to AD research has a potentially large societal value. AD is among the leading causes of disability and death in older people. According to the Alzheimer’s Association, four million Americans currently suffer from AD. That number is expected to escalate to over 10 million in coming decades. Patients progress from memory loss to a bedridden state over many years and require ... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2364569 Thu, 29 Nov 2007 05:00:00 +0100 2364569 http://www.medworm.com/index.php?rid=2364568&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_13 Neuroanatomical informatics, a subspecialty of neuroinformatics, focuses on technological solutions to neuroimage database access. Its current main goal is an image-based query system that is able to retrieve imagery based on anatomical location. Here, we describe a set of tools that collectively form such a solution for sectional material and that are available to investigators to use on their own data sets. The system accepts slide images as input and yields a matrix of transformation parameters that map each point on the input image to a standardized 3D brain atlas. In essence, this spatial normalization makes the atlas a spatial indexer from which queries can be issued simply by specifying a location on the reference atlas. Our objective here is to familiarize potential users of the sy... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=2364568 Thu, 29 Nov 2007 05:00:00 +0100 2364568 http://www.medworm.com/index.php?rid=1538346&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_12 This chapter describes the use of high-resolution functional magnetic resonance imaging (fMRI) technology in brain odor mapping and a suite of informatics tools for building, databasing, and analyzing fMRI odor maps. OdorMapBuilder is a software program that extracts the olfactory signals that occurred in a particular layer of the olfactory bulb (OB), that is, the glomerular layer, from the 3D imaging data and generates 2D flat odor maps. Odor maps describe the odor-induced spatial activity patterns in the entire glomerular layer in the OB. OdorMapDB is a Web-based database system that serves as a centralized repository for the fMRI odor maps. OdorMapComparer is a software program that allows users to visually evaluate and statistically determine the similarity or difference between two fM... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538346 Thu, 29 Nov 2007 05:00:00 +0100 1538346 http://www.medworm.com/index.php?rid=1538345&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_8 A key challenge for neuroinformatics is to devise methods for representing, accessing, and integrating vast amounts of diverse and complex data. A useful approach to represent and integrate complex data sets is to develop mathematical models [Arbib (The Handbook of Brain Theory and Neural Networks, pp. 741–745, 2003); Arbib and Grethe (Computing the Brain: A Guide to Neuroinformatics, 2001); Ascoli (Computational Neuroanatomy: Principles and Methods, 2002); Bower and Bolouri (Computational Modeling of Genetic and Biochemical Networks, 2001); Hines et al. (J. Comput. Neurosci. 17, 7–11, 2004); Shepherd et al. (Trends Neurosci. 21, 460–468, 1998); Sivakumaran et al. (Bioinformatics 19, 408–415, 2003); Smolen et al. (Neuron 26, 567&ndash... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538345 Thu, 29 Nov 2007 05:00:00 +0100 1538345 http://www.medworm.com/index.php?rid=1538344&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_10 The electrical activity of individual neurons and neuronal networks is shaped by the complex interplay of a large number of non-linear processes, including the voltage-dependent gating of ion channels and the activation of synaptic receptors. These complex dynamics make it difficult to understand how individual neuron or network parameters—such as the number of ion channels of a given type in a neuron’s membrane or the strength of a particular synapse—influence neural system function. Systematic exploration of cellular or network model parameter spaces by computational brute force can overcome this difficulty and generate comprehensive data sets that contain information about neuron or network behavior for many different combinations of parameters. Searching such data set... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538344 Thu, 29 Nov 2007 05:00:00 +0100 1538344 http://www.medworm.com/index.php?rid=1538343&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_18 The search for DNA alterations that cause human disease has been an area of active research for more than 50 years, since the time that the genetic code was first solved. In the absence of data implicating chromosomal aberrations, researchers historically have performed whole genome linkage analysis or candidate gene association analysis to develop hypotheses about the genes that most likely cause a specific phenotype or disease. Whereas whole genome linkage analysis examines all chromosomal locations without a priori predictions regarding what genes underlie susceptibility, candidate gene association studies require a researcher to know in advance the genes that he or she wishes to test (based on their knowledge of a disease). To date, very few whole genome linkage studies and candidate g... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538343 Thu, 29 Nov 2007 05:00:00 +0100 1538343 http://www.medworm.com/index.php?rid=1538342&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_15 Receptor distributions in the brain are studied by autoradiographic mapping in brain slices, which is a labor-intensive and expensive procedure. To keep track of the results of such studies, we have designed CoReDat, a multi-user relational database system that is available for download from www.cocomac.org/coredat. Here, we describe the data model and provide an architectural overview of CoReDat for the neuroscientist who wants to use this database, adapt it for related purposes, or build a new one. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538342 Thu, 29 Nov 2007 05:00:00 +0100 1538342 http://www.medworm.com/index.php?rid=1538341&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_3 To determine effective database architecture for a specific neuroscience application, one must consider the distinguishing features of research databases and the requirements that the particular application must meet. Research databases manage diverse types of data, and their schemas evolve fairly steadily as domain knowledge advances. Database search and controlled-vocabulary access across the breadth of the data must be supported. We provide examples of design principles employed by our group as well as others that have proven successful and also introduce the appropriate use of entity–attribute–value (EAV) modeling. Most important, a robust architecture requires a significant metadata component, which serves to describe the individual types of data in terms of function and p... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538341 Thu, 29 Nov 2007 05:00:00 +0100 1538341 http://www.medworm.com/index.php?rid=1538340&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_17 A critical goal of neuroscience is to fully understand neural processes and their relations to mental processes, and cognitive, affective, and behavioral disorders. Computational modeling, although still in its infancy, continues to play a central role in this endeavor. Presented here is a review of different aspects of computational modeling that help to explain many features of neuropsychological syndromes and psychiatric disease. Recent advances in computational modeling of epilepsy, cortical reorganization after lesions, Parkinson’s and Alzheimer diseases are also reviewed. Additionally, this chapter will also identify some trends in the computational modeling of brain functions. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538340 Thu, 29 Nov 2007 05:00:00 +0100 1538340 http://www.medworm.com/index.php?rid=1538339&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_14 Analysis of functional and structural magnetic resonance imaging (MRI) brain images requires a complex sequence of data processing steps to proceed from raw image data to the final statistical tests. Neuroimaging researchers have begun to apply workflow-based computing techniques to automate data analysis tasks. This chapter discusses eight major components of workflow management systems (WFMSs): the workflow description language, editor, task modules, data access, verification, client, engine, and provenance, and their implementation in the Fiswidgets neuroimaging workflow system. Neuroinformatics challenges involved in applying workflow techniques in the domain of neuroimaging are discussed. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538339 Thu, 29 Nov 2007 05:00:00 +0100 1538339 http://www.medworm.com/index.php?rid=1538338&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_11 Quantifying the effect of a genetic manipulation or disease is a complicated process in a population of animals. Probabilistic brain atlases can capture population variability and be used to quantify those variations in anatomy as measured by structural imaging. Minimum deformation atlases (MDAs), a subclass of probabilistic atlases, are intensity-based averages of a collection of scans in a common space unbiased by selection of a single target image. Here, we describe a method for generating an MDA from a set of magnetic resonance microscopy images. First, the images are segmented to remove any non-brain tissue and bias field corrected to remove field inhomogeneities. The corrected images are then linearly aligned to a representative scan, the geometric mean of all the transformations is ... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538338 Thu, 29 Nov 2007 05:00:00 +0100 1538338 http://www.medworm.com/index.php?rid=1538337&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_7 The GEneral NEural SImulation System (GENESIS) is an open source simulation platform for realistic modeling of systems ranging from subcellular components and biochemical reactions to detailed models of single neurons, simulations of large networks of realistic neurons, and systems-level models. The graphical interface XODUS permits the construction of a wide variety of interfaces for the control and visualization of simulations. The object-oriented scripting language allows one to easily construct and modify simulations built from the GENESIS libraries of simulation components. Here, we present procedures for installing GENESIS and its supplementary tutorials, running GENESIS simulations, and creating new neural simulations. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538337 Thu, 29 Nov 2007 05:00:00 +0100 1538337 http://www.medworm.com/index.php?rid=1538336&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_16 We outline the theory behind complex trait analysis and systems genetics and describe web-accessible resources including GeneNetwork (GN) that can be used for rapid exploratory analysis and hypothesis testing. GN, in particular, is a tightly integrated suite of bioinformatics tools and data sets, which supports the investigation of complex networks of gene variants, molecules, and cellular processes that modulate complex traits, including behavior and disease susceptibility. Using various statistical tools, users are able to analyze gene expression in various brain regions and tissues, map loci that modulate these traits, and explore genetic covariance among traits. Taken together, these tools enable the user to begin to assess complex interactions of gene networks, and facilitate analysis... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538336 Thu, 29 Nov 2007 05:00:00 +0100 1538336 http://www.medworm.com/index.php?rid=1538335&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_2 Data interoperability between well-defined domains is currently performed by leveraging Web services. In the biosciences, more specifically in neuroscience, robust data interoperability is more difficult to achieve due to data heterogeneity, continuous domain changes, and the constant creation of new semantic data models (Nadkarni et al., J Am Med Inform Assoc 6, 478–93, 1999; Miller et al., J Am Med Inform Assoc 8, 34–48, 2001; Gardner et al., J Am Med Inform Assoc 8, 17–33, 2001). Data heterogeneity in neurosciences is primarily due to its multidisciplinary nature. This results in a compelling need to integrate all available neuroscience information to improve our understanding of the brain. Researchers associated with neuroscience initiatives such as the human brain pr... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538335 Thu, 29 Nov 2007 05:00:00 +0100 1538335 http://www.medworm.com/index.php?rid=1538334&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_5 The insufficiency of terminological standards in neuroscience is increasingly recognized as a serious obstacle to interoperability. Adoption of a controlled vocabulary is a successful solution for small numbers of groups that work closely together but is impractical for large numbers of groups who represent diverse areas of research, index information by various legitimate nomenclatures, or publish in different languages. Interoperability among such disparate databases requires a translation mechanism, or “mediator,” to enable communication and data sharing among databases. Shared ontologies are essential components of a mediator. An ontology codifies the relations between terms of multiple nomenclatures and the concepts they represent. Neuroanatomy is central to neuroscience, ... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538334 Thu, 29 Nov 2007 05:00:00 +0100 1538334 http://www.medworm.com/index.php?rid=1538333&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_19 The Alzheimer Research Forum Web site ( http://www.alzforum.org ) is an independent research project to develop an online community resource to manage scientific knowledge, information, and data about Alzheimer disease (AD). Its goals are to promote rapid communication, research efficiency, and collaborative, multidisciplinary interactions. Introducing new knowledge management approaches to AD research has a potentially large societal value. AD is among the leading causes of disability and death in older people. According to the Alzheimer’s Association, four million Americans currently suffer from AD. That number is expected to escalate to over 10 million in coming decades. Patients progress from memory loss to a bedridden state over many years and require ... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538333 Thu, 29 Nov 2007 05:00:00 +0100 1538333 http://www.medworm.com/index.php?rid=1538332&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_13 Neuroanatomical informatics, a subspecialty of neuroinformatics, focuses on technological solutions to neuroimage database access. Its current main goal is an image-based query system that is able to retrieve imagery based on anatomical location. Here, we describe a set of tools that collectively form such a solution for sectional material and that are available to investigators to use on their own data sets. The system accepts slide images as input and yields a matrix of transformation parameters that map each point on the input image to a standardized 3D brain atlas. In essence, this spatial normalization makes the atlas a spatial indexer from which queries can be issued simply by specifying a location on the reference atlas. Our objective here is to familiarize potential users of the sy... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538332 Thu, 29 Nov 2007 05:00:00 +0100 1538332 http://www.medworm.com/index.php?rid=1538331&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_9 Data integration is particularly difficult in neuroscience; we must organize vast amounts of data around only a few fragmentary functional hypotheses. It has often been noted that computer simulation, by providing explicit hypotheses for a particular system and bridging across different levels of organization, can provide an organizational focus, which can be leveraged to form substantive hypotheses. Simulations lend meaning to data and can be updated and adapted as further data come in. The use of simulation in this context suggests the need for simulator adjuncts to manage and evaluate data. We have developed a neural query system (NQS) within the NEURON simulator, providing a relational database system, a query function, and basic data-mining tools. NQS is used within the simulation con... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538331 Thu, 29 Nov 2007 05:00:00 +0100 1538331 http://www.medworm.com/index.php?rid=1538330&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_1 Processing text from scientific literature has become a necessity due to the burgeoning amounts of information that are fast becoming available, stemming from advances in electronic information technology. We created a program, NeuroText ( http://senselab.med.yale.edu/textmine/neurotext.pl ), designed specifically to extract information relevant to neuroscience-specific databases, NeuronDB and CellPropDB ( http://senselab.med.yale.edu/senselab/ ), housed at the Yale University School of Medicine. NeuroText extracts relevant information from the Neuroscience literature in a two-step process: each step parses text at different levels of granularity. NeuroText uses an expert-mediated knowledgebase and combines the techniques of indexing, c... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538330 Thu, 29 Nov 2007 05:00:00 +0100 1538330 http://www.medworm.com/index.php?rid=1538329&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_6 One of the more important recent additions to the NEURON simulation environment is a tool called ModelView, which simplifies the task of understanding exactly what biological attributes are represented in a computational model. Here, we illustrate how ModelView contributes to the understanding of models and discuss its utility as a neuroinformatics tool for analyzing models in online databases and as a means for facilitating interoperability among simulators in computational neuroscience. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538329 Thu, 29 Nov 2007 05:00:00 +0100 1538329 http://www.medworm.com/index.php?rid=1538328&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-59745-520-6_4 EXtensible Markup Language (XML) technology provides an ideal representation for the complex structure of models and neuroscience data, as it is an open file format and provides a language-independent method for storing arbitrarily complex structured information. XML is composed of text and tags that explicitly describe the structure and semantics of the content of the document. In this chapter, we describe some of the common uses of XML in neuroscience, with case studies in representing neuroscience data and defining model descriptions based on examples from NeuroML. The specific methods that we discuss include (1) reading and writing XML from applications, (2) exporting XML from databases, (3) using XML standards to represent neuronal morphology data, (4) using XML to represent experimen... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538328 Thu, 29 Nov 2007 05:00:00 +0100 1538328 http://www.medworm.com/index.php?rid=1538352&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-099-1_6 (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538352 Tue, 13 Nov 2007 05:00:00 +0100 1538352 http://www.medworm.com/index.php?rid=1538351&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-099-1_4 (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538351 Tue, 13 Nov 2007 05:00:00 +0100 1538351 http://www.medworm.com/index.php?rid=1538350&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-099-1_7 (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538350 Tue, 13 Nov 2007 05:00:00 +0100 1538350 http://www.medworm.com/index.php?rid=1538349&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-099-1_8 The blood–brain barrier (BBB) plays a crucial regulatory role in central nervous system (CNS) function and in communication between the CNS and the periphery. In addition to lipophilic molecules, many small proteins are now known to cross the BBB. Such recognition was expedited by techniques that quantify the influx and efflux of peptides and polypeptides across the BBB of the living animal. These methods are described in this review. Their use has enhanced our knowledge of the crucial link between the CNS and the rest of the body, and this has physiological and pathological implications as well as therapeutic potential. (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538349 Tue, 13 Nov 2007 05:00:00 +0100 1538349 http://www.medworm.com/index.php?rid=1538348&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-099-1_5 (Source: Springer protocols feed by Neuroscience) Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538348 Tue, 13 Nov 2007 05:00:00 +0100 1538348 http://www.medworm.com/index.php?rid=1538347&cid=s_37128_168_f&fid=37128&url=http%3A%2F%2Fwww.springerprotocols.com%2FAbstract%2Fdoi%2F10.1007%2F978-1-60327-099-1_2 Activity-dependent neuroprotective protein (ADNP, human calculated molecular mass 123,562.8 Da) is a newly discovered glial protein that it is essential for embryonic development and brain formation. ADNP includes an active neuroprotective site, an 8 amino acid peptide NAPSVIPQ (NAP). The current study was set out to prepare antibodies to ADNP that will recognize different sites on the molecule. Four peptides of 8–20 amino acids that span the ADNP molecule, including NAPVSIPQ, were prepared. Peptides (containing a Cys residue attached to the N-terminal amino acid) were conjugated to keyhole limpet hemocyanin (KLH) and injected to respective rabbits in the presence of Freund’s complete adjuvant. Following five booster injections in incomplete Freund’s adjuvant, the ... Springer protocols feed by Neuroscience info http://www.medworm.com/rss/comments.php?id=1538347 Tue, 13 Nov 2007 05:00:00 +0100 1538347