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Optogenetic signaling inhibitors for studying brain plasticity

用于研究大脑可塑性的光遗传学信号抑制剂

基本信息

批准号：
9353464
负责人：
WENBIAO GAN
金额：
$ 45.9万
依托单位：
MAX PLANCK FLORIDA CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-15 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9353464
关键词：
Animals Behavioral Biochemical Brain Collaborations Cyclic AMP-Dependent Protein Kinases Data Dendritic Spines Disease Event Excitatory Synapse Fright Goals Hippocampus (Brain)Hour Image Knowledge Learning Learning Disabilities Light Mediating Memory Mental disorders Molecular Molecular Conformation Mus Neurons Oxygen Peptides Performance Pharmaceutical Preparations Pharmacology Phosphotransferases Protein Kinase Inhibitors Proteins Psyche structure Research Signal Pathway Signal Transduction Slice Synapses Synaptic plasticity Techniques Testing Time Translating Vertebral column absorption base behavioral plasticity calmodulin-dependent protein kinase II design genetic manipulation improved in vivo inhibitor/antagonist insight kinase inhibitor learning extinction neuronal circuitry optogenetics postsynaptic protein kinase inhibitor spatiotemporal tool tool development voltage

项目摘要

Project Summary/Abstract Synaptic plasticity is thought to be a basis of learning and memory of the brain. Signaling mechanisms underlying synaptic and behavioral plasticity have been extensively studied with the aid of pharmacological and genetic manipulation of signaling. However, it has been difficult to assess the spatiotemporal aspects of signaling activity particularly. The goal of this proposal is to develop a new technique based on genetically encoded light- inducible kinase inhibitors to resolve the spatiotemporal dynamics of signaling required for synaptic and behavioral plasticity in vivo. Our preliminary data using a newly- developed photo-inducible CaMKII inhibitor demonstrates that ~60 s of CaMKII activity is sufficient to induce structural plasticity of dendritic spines. We aim to 1) develop photo- inducible inhibitors for kinases including CaMKII, PKC and PKA, 2) determine the timing of kinase activity required for synaptic plasticity in slices, and 3) identify the spatiotemporal window of kinase activity required for learning-related dendritic spine turnover in vivo and animal’s performance improvement after learning. The new tool will provide new insights into the action of kinases in vivo during synaptic and behavioral plasticity.

项目概要/摘要突触可塑性被认为是大脑学习和记忆的基础。信令突触和行为可塑性的机制已被广泛研究借助信号传导的药理学和遗传操作。然而，它有特别是很难评估信号活动的时空方面。这该提案的目标是开发一种基于基因编码光的新技术诱导型激酶抑制剂解决信号传导所需的时空动态用于体内突触和行为可塑性。我们的初步数据使用了新的- 开发的光诱导 CaMKII 抑制剂表明，约 60 秒的 CaMKII 活性足以诱导树突棘的结构可塑性。我们的目标是 1) 开发照片- 激酶的诱导型抑制剂，包括 CaMKII、PKC 和 PKA，2) 确定时机切片中突触可塑性所需的激酶活性，以及 3) 确定学习相关树突棘所需的激酶活性时空窗口体内周转率和动物学习后表现的改善。新工具将为体内激酶在突触和行为过程中的作用提供新的见解可塑性。