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

• 批准号: 10403567
• 负责人: SCOTT H SODERLING
• 金额: $ 54.08万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 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/10403567
• 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); Etiology; Event; Family; Fractionation; Future; Gene Mutation; Genetic; Genome engineering; Goals; Grant; Hippocampus (Brain); Human; Image; In Vitro; Knowledge; Label; Lead; Learning; Link; Mass Spectrum Analysis; Mediating; Memory; Methods; Molecular; Mus; Mutation; Nature; Neurodevelopmental Disorder; Neurons; Pathway interactions; Pharmacology; Physiology; Presynaptic Terminals; Problem Solving; Process; Property; Proteins; Proteome; Proteomics; Regulation; Role; Signal Pathway; Signal Transduction; Signaling Molecule; Structure; Synapses; Synapsins; Synaptic Transmission; Synaptic Vesicles; Synaptosomes; Testing; Therapeutic; Time; Transgenic Mice; United States National Institutes of Health; Vertebral column; Vesicle; base; behavior test; cell type; cytomatrix; depolymerization; follow-up; functional plasticity; genome editing; in vivo; innovation; insight; mutant; novel strategies; optogenetics; postsynaptic; presynaptic; protein complex; response; rho; time use; tool; two-photon

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