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Mechanisms of synaptic plasticity and memory

突触可塑性和记忆机制

基本信息

批准号：
8443811
负责人：
Mauro Costa-Mattioli
金额：
$ 37.56万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8443811
关键词：
Actins Address Aging Alzheimer&apos s Disease Architecture Behavioral Biochemical Biological Assay Brain Centrifugation Cognition Disorders Companions Complex Cytoskeleton Data Dendritic Spines Down Syndrome Event F-Actin Fragile X Syndrome Functional disorder G Actin Genetic Guanosine Triphosphate Phosphohydrolases Hippocampus (Brain)Hour Huntington Disease Image Knowledge Lead Learning Link Long-Term Depression Measures Mediating Memory Memory Loss Modification Molecular Morphology Mus Nature Neurodegenerative Disorders Neurodevelopmental Disorder Neurons Parkinsonian Disorders Pathway interactions Pharmacogenetics Phase Phosphorylation Process Prosencephalon Protein Biosynthesis Proteins Protocols documentation Rett Syndrome Role Series Shapes Short-Term Memory Signal Pathway Signal Transduction Sirolimus Slice Staining method Stains Stream Synapses Synaptic plasticity Testing Training Transgenic Organisms Tuberous sclerosis protein complex Vertebral column Western Blotting Wild Type Mouse age related behavior test cofilin conditioned fear density developmental disease genetic regulatory protein human FRAP1 protein insight interdisciplinary approach jasplakinolide long term memory mTOR protein morris water maze polymerization synaptic function

项目摘要

DESCRIPTION (provided by applicant): Little is known about the molecular and cellular mechanisms underlying actin dynamic-mediated changes in synaptic strength and memory formation. Here we propose to test the hypothesis that the regulatory mammalian target of rapamycin complex 2 (mTORC2) is the link between synaptic activity and actin cytoskeleton restructuring involved in synaptic plasticity and memory formation. Since mTORC2 was only recently discovered, relatively little is known about its function, including how it is regulated ad the nature of its downstream targets in the brain. This proposal combines biochemical, transgenic, pharmacological, electrophysiological, imaging, and behavioral approaches to explore several crucial aspects of mTORC2 function in the brain including: a) its role in synaptic plasticity and memory, b) the up-stream synaptic events which activate mTORC2, and c) the downstream molecular mechanisms by which mTORC2 regulates long- term synaptic plasticity and long-term memory. This study will provide insight into the basic molecular and cellular mechanisms underlying learning and memory, possibly leading to new treatments for conditions associated with memory dysfunction such as aging, developmental and neurodegenerative disorders, all conditions in which mTORC2 activity is altered.

描述（由申请人提供）：关于肌动蛋白动力学介导的突触强度和记忆形成变化的分子和细胞机制知之甚少。在这里，我们建议验证这样的假设：雷帕霉素复合物2（mTORC 2）的哺乳动物调节靶点是突触活性与参与突触可塑性和记忆形成的肌动蛋白细胞骨架重组之间的联系。由于mTORC2是最近才发现的，因此对其功能知之甚少，包括其如何调节以及其在大脑中下游靶点的性质。该提议结合生物化学、转基因、药理学、电生理学、成像和行为方法来探索mTORC 2在脑中功能的几个关键方面，包括：a）其在突触可塑性和记忆中的作用，B）激活mTORC 2的上游突触事件，和c）mTORC 2调节长期突触可塑性和长期记忆的下游分子机制。这项研究将深入了解学习和记忆的基本分子和细胞机制，可能导致与记忆功能障碍相关的疾病的新治疗方法，如衰老，发育和神经退行性疾病，所有mTORC 2活性改变的疾病。