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Virtually all scientific problems in Neuroscience require mathematical analysis, and all neuroscientists are increasingly required to have a significant understanding of mathematical methods. There is currently no comprehensive, integrated introductory book on the use of mathematics in Neuroscience, existing books either concentrate solely on theoretical modeling or discuss mathematical concepts for the treatment of very specific problems. This book fills this need by systematically introducing mathematical and computational tools in precisely the contexts that first established their importance for neuroscience.

During the initial stages of hemorrhagic stroke, including intracerebral hemorrhage and subarachnoid hemorrhage, the reflex mechanisms are activated to protect cerebral perfusion, but secondary dysfunction of cerebral flow autoregulation will eventually reduce global cerebral blood flow and the delivery of metabolic substrates, leading to generalized cerebral ischemia, hypoxia, and ultimately, neuronal cell death. Cerebral blood flow is controlled by various regulatory mechanisms, including prevailing arterial pressure, intracranial pressure, arterial blood gases, neural activity, and metabolic demand. Evoked by the concept of vascular neural network, the unveiled neural vascular mechanism gains more and more attentions. Astrocyte, neuron, pericyte, endothelium, and so forth are formed as a communicate network to regulate with each other as well as the cerebral blood flow. However, the signaling molecules responsible for this communication between these new players and blood vessels are yet to be definitively confirmed. Recent evidence suggested the pivotal role of transcriptional mechanism, including but not limited to miRNA, lncRNA, exosome, and so forth, for the cerebral blood flow autoregulation. In the present review, we sought to summarize the hemodynamic changes and underline neural vascular mechanism for cerebral blood flow autoregulation in stroke-prone state and after hemorrhagic stroke and hopefully provide more systematic and innovative research interests for the pathophysiology and therapeutic strategies of hemorrhagic stroke.

Genes involved in synaptic plasticity, particularly genes encoding postsynaptic density proteins, have been recurrently linked to psychiatric disorders including schizophrenia and autism. Postsynaptic density Homer1 proteins contribute to synaptic plasticity through the competing actions of short and long isoforms. The activity-induced expression of short Homer1 isoforms, Homer1a and Ania-3, is thought to be related to processes of learning and memory. However, the precise regulation of Homer1a and Ania-3 with different components of learning has not been investigated. Here, we used in situ hybridization to quantify short and long Homer1 expression in the hippocampus following consolidation, retrieval, and extinction of associative fear memory, using contextual fear conditioning in rats. Homer1a and Ania-3, but not long Homer1, were regulated by contextual fear learning or novelty detection, although their precise patterns of expression in hippocampal subregions were dependent on the isoform. We also show for the first time that the two short Homer1 isoforms are regulated after the retrieval and extinction of contextual fear memory, albeit with distinct temporal and spatial profiles. These findings support a role of activity-induced Homer1 isoforms in learning and memory processes in discrete hippocampal subregions and suggest that Homer1a and Ania-3 may play separable roles in synaptic plasticity.

Benzodiazepine tranquilizers are used in the treatment of anxiety disorders. To identify the molecular and neuronal target mediating the anxiolytic action of benzodiazepines, we generated and analyzed two mouse lines in which the α2 or α3 GABAA(γ-aminobutyric acid type A) receptors, respectively, were rendered insensitive to diazepam by a knock-in point mutation. The anxiolytic action of diazepam was absent in mice with the α2(H101R) point mutation but present in mice with the α3(H126R) point mutation. These findings indicate that the anxiolytic effect of benzodiazepine drugs is mediated by α2 GABAAreceptors, which are largely expressed in the limbic system, but not by α3 GABAAreceptors, which predominate in the reticular activating system.

Neuromodulation will be the first comprehensive and in-depth reference textbook covering all aspects of the rapidly growing field of neuromodulation.This book provides a complete discussion of the fundamental principles of neuromodulation and therapies applied to the brain, spinal cord, peripheral nerves, autonomic nerves and various organs.

Angiotensin II Type 1 Receptor Signaling Contributes to Synaptophysin Degradation and Neuronal Dysfunction in the Diabetic Retina Toshihide Kurihara 1 2 3 , Yoko Ozawa 1 2 3 , Norihiro Nagai 1 2 , Kei Shinoda 4 , Kousuke Noda 1 2 , Yutaka Imamura 5 , Kazuo Tsubota 2 , Hideyuki Okano 3 , Yuichi Oike 6 and Susumu Ishida 1 2 1 Laboratory of Retinal Cell Biology, Keio University School of Medicine, Tokyo, Japan 2 Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan 3 Department of Physiology, Keio University School of Medicine, Tokyo, Japan 4 Department of Ophthalmology, Oita University Faculty of Medicine, Hasama-machi, Yufu-shi, Oita, Japan 5 Inaida Laboratory for Anti-Aging Medicine, Keio University School of Medicine, Tokyo, Japan 6 Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan Corresponding author: Susumu Ishida, ishidasu{at}sc.itc.keio.ac.jp Abstract OBJECTIVE— Pathogenic mechanisms underlying diabetes-induced retinal dysfunction are not fully understood. The aim of the present study was to show the relationship of the renin-angiotensin system (RAS) with the synaptic vesicle protein synaptophysin and neuronal activity in the diabetic retina. RESEARCH DESIGN AND METHODS— C57BL/6 mice with streptozotocin-induced diabetes were treated with the angiotensin II type 1 receptor (AT1R) blocker telimsartan or valsartan, and retinal function was analyzed by electroretinography. Retinal production of the RAS components and phosphorylation of ERK (extracellular-signal regulated kinase) were examined by immunoblotting. Retinal mRNA and protein levels of synaptophysin were measured by quantitative RT-PCR and immunoblot analyses, respectively. In vitro, synaptophysin levels were also evaluated using angiotensin II–stimulated PC12D neuronal cells cultured with or without the inhibition of ERK signaling or the ubiquitin-proteasome system (UPS). RESULTS— Induction of diabetes led to a significant increase in retinal production of angiotensin II and AT1R together with ERK activation in the downstream of AT1R. AT1R blockade significantly reversed diabetes-induced electroretinography changes and reduction of synaptophysin protein, but not mRNA, levels in the diabetic retina. In agreement with the AT1R-mediated posttranscriptional downregulation of synaptophysin in vivo, in vitro application of angiotensin II to PC12D neuronal cells caused the UPS–mediated degradation of synaptophysin protein via AT1R, which proved to be induced by ERK activation. CONCLUSIONS— These data indicate the first molecular evidence of the RAS-induced synaptophysin degradation and neuronal dysfunction in the diabetic retina, suggesting the possibility of the AT1R blockade as a novel neuroprotective treatment for diabetic retinopathy. Footnotes Published ahead of print at http://diabetes.diabetesjournals.org on 16 May 2008. T.K. and Y.O. contributed equally to this work. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted May 12, 2008. Received September 11, 2007. DIABETES

Handbook of the Behavioral Neurobiology of Serotonin, Second Edition, builds on the success of the first edition by continuing to provide a detailed and comprehensive overview of the many facets of behavioral serotonin research. The text expands on the two key topics, behavioral control (sensory processing, ultrasonic vocalization, and melatonin and sleep control) and psychiatric disorders, including its role on psychostimulant abuse and addiction. The new edition includes two new sections on the serotonin systems interactions and the involvement of serotonin in neurological disorders and associated treatment. Serotonin is a major neurotransmitters in the serotonergic system which one of the best studied and understood transmitter systems. Both are critically involved in the organization of all behaviors and in the regulation of emotion and mood.