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.

项目摘要/摘要突触可塑性被认为是学习和记忆大脑的基础。信号突触和行为可塑性的基础机制已广泛研究借助信号传导的药物和基因操纵。但是，它有他很难特别评估信号活性的时空方面。这该建议的目标是开发一种基于基因编码光的新技术可诱导激酶抑制剂解决所需信号传导的时空动力学用于体内突触和行为可塑性。我们的初步数据使用新近开发的照片诱导型CAMKII抑制剂表明，CAMKII的活性约为60 s 我们的目的是1）开发照片 - 包括CAMKII，PKC和PKA在内的激酶的诱导抑制剂，2）确定时间安排切片中突触可塑性所需的激酶活性，3）确定与学习相关的树突脊柱所需的激酶活性的时空窗口体内的营业额和动物学习后的性能提高。新工具将对激酶在突触和行为过程中的体内作用提供新的见解可塑性。