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Activity-dependent Synaptic and Circuit Plasticity

活动依赖性突触和电路可塑性

基本信息

批准号：
9220657
负责人：
ROBERT C MALENKA
金额：
$ 195.15万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2020-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9220657
关键词：
AMPA Receptors Address Area Autistic Disorder Behavior Binding Biochemical Biological Assay Bipolar Disorder Brain Brain Diseases Calcium Cell Adhesion Molecules Cell Communication Cell membrane Cells Communication Communities Dendritic Spines Development Effectiveness Electrophysiology (science)Excitatory Synapse Family Fiber Functional disorder Generations Genetic study Goals Growth Hippocampus (Brain)Human Genetics Image Individual Integral Membrane Protein Interneurons Knock-out Knockout Mice Knowledge Lead Learning Leucine-Rich Repeat Life Experience Long-Term Potentiation Maintenance Mediating Memory Mental disorders Modernization Modification Molecular Molecular Genetics Mus Mutation Neurons Neurosciences Neurosciences Research Normal Range Pathogenesis Pathologic Photometry Play Population Principal Investigator Process Proteins Reagent Research Research Personnel Role Schizophrenia Signal Transduction Synapses Synaptic plasticity Thinking Tretinoin addiction autism spectrum disorder behavioral plasticity biological research cell type experience genetic manipulation imaging approach innovation insight knock-down neural circuit neuronal excitability neurotransmitter release novel outreach postsynaptic presynaptic public health relevance relating to nervous system success symposium synaptotagmin synaptotagmin I synaptotagmin VII tool trafficking web site

项目摘要

DESCRIPTION (provided by applicant): The brain processes information and generates behavior by transmitting signals at its synapses, which connect neurons into vast networks of communicating cells. These networks, known as neural circuits, are not static but are modified throughout life by experience. Such neural circuit plasticity is critical for the brain to develop normally and perform all of its important functions, including learning and memory. When brain plasticity mechanisms function abnormally, however, devastating mental illnesses often ensue. Thus, a major goal of neuroscience research is to understand the detailed mechanisms by which the brain activity generated by experiences modifies neural circuit behavior. This occurs in large part because neural activity continually adjusts the efficiency or strength of synaptic communication between neurons, a process known as synaptic plasticity. Despite the importance of synaptic plasticity for brain development and higher brain functions, relatively litte is known about its molecular mechanisms other than it is commonly triggered by activity- dependent changes in intracellular calcium levels. This Conte Center will bring together four leading investigators to continue their previous efforts to use innovative molecular genetic manipulations combined with sophisticated and unique biochemical, electrophysiological, and imaging assays to elucidate highly novel mechanisms that underlie different forms of synaptic plasticity and how these forms of synaptic plasticity play a role in adaptive and pathological forms of experience-dependent plasticity, including learning and memory. The new insights into synaptic and circuit plasticity mechanisms generated by this Conte Center will influence a broad array of neuroscientists working on a wide range of topics related to normal and pathological brain function. The Center will also provide the research community with novel molecular genetic tools and genetically modified mice that can be used to manipulate proteins critical for synaptic plasticity throughout the brain to explore the roles of these critical proteins in specifi cell types that participate in a wide range of normal and pathological behaviors. Thus the Center will provide both technological and intellectual innovations to one of the most important areas of neuroscience research with far ranging implications for our understanding of normal and diseased brain function. Relevance The effectiveness of communication between nerve cells is modified by experience and these modifications are crucial for all normal brain functions including learning and memory. The goal of this Center is to determine the molecular mechanisms that are responsible for these modifications. Such information will lead to a better understanding of the causes of mental illness and eventually to the development of more efficacious treatments