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Proteomic and Functional Analysis of Presynaptic Physiology and Plasticity

突触前生理学和可塑性的蛋白质组学和功能分析

基本信息

批准号：
10591544
负责人：
SCOTT H SODERLING
金额：
$ 51.34万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-10 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10591544
关键词：
Actins Action Potentials Basic Science Behavior Biotin Biotinylation Brain Diseases CRISPR/Cas technology Clustered Regularly Interspaced Short Palindromic Repeats Complex Coupled Coupling Cytoskeleton Data Development Disease Electrophysiology (science)Elements Etiology Event Family Fractionation Future Gene Mutation Genetic Genome engineering Goals Grant Hippocampus Human Image In Vitro Knowledge Label Learning Link Mass Spectrum Analysis Mediating Memory Methods Molecular Mus Mutation Nature Neurodevelopmental Disorder Neurons Pathway interactions Physiology Presynaptic Terminals Process Property Proteins Proteome Proteomics Regulation Role Signal Pathway Signal Transduction Signaling Molecule Structure Synapses Synapsins Synaptic Transmission Synaptic Vesicles Synaptic plasticity Synaptosomes Testing Therapeutic Time Transgenic Mice United States National Institutes of Health Vertebral column Vesicle behavior test cell type cytomatrix follow-up functional plasticity genome editing in vivo innovation insight mutant novel strategies optogenetics pharmacologic postsynaptic presynaptic protein complex response rho synaptic function time use tool two-photon

项目摘要

ABSTRACT The molecular mechanisms of plasticity within the presynapse and its role in behaviors such as learning and memory are still poorly understood, mainly due to a lack of knowledge of the signaling molecules of the presynaptic cytomatrix and tools to spatially and temporally manipulate presynaptic plasticity. This gap in knowledge is a fundamental barrier to the field. In this project, we will develop and utilize innovative proteomic, genome editing, and optogenetic approaches to solve these problems, revealing the proteins and inner workings of the cytomatrix of presynapses from distinct neuronal cell types and their roles in learning and memory. We anticipate these data will provide a new and unparalleled molecular framework for future studies on presynaptic physiology as well as insights into how forms of presynaptic plasticity modulate behavior.

摘要突触前可塑性的分子机制及其在学习和学习等行为中的作用记忆仍然知之甚少，主要是由于缺乏对大脑中信号分子的了解。突触前细胞矩阵和在空间和时间上操纵突触前可塑性的工具。这一差距在知识是这一领域的根本障碍。在这个项目中，我们将开发和利用创新的蛋白质组学，基因组编辑和光遗传学方法来解决这些问题，揭示蛋白质和内部工作原理来自不同神经细胞类型的突触前细胞矩阵及其在学习和记忆中的作用。我们预计这些数据将为未来对突触前的研究提供一个新的、无与伦比的分子框架生理学以及对突触前可塑性如何调节行为的洞察。