Mechanisms of synaptic plasticity and memory

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，我们建议测试的假设，雷帕霉素复合物2（mTORC2）的调节哺乳动物靶是突触活动和肌动蛋白细胞骨架重组参与突触可塑性和记忆形成之间的联系。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。

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.