Single-Synapse Analysis of Neocortical Circuit Plasticity

新皮质回路可塑性的单突触分析

基本信息

批准号：
8505730
负责人：
Stephen J Smith
金额：
$ 6.5万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8505730
关键词：
Adhesions Biological Models Brain Characteristics Data Dendritic Spines Development Disease Drug Delivery Systems Dyes Environment Exhibits Experimental Designs Future Glutamates Goals Homeostasis Individual Injection of therapeutic agent Injury Knowledge Learning Link Logic Maps Measurement Measures Memory Memory Disorders Methods Modification Molecular Molecular Profiling Mus Neocortex Nerve Degeneration Neurodegenerative Disorders Neurodevelopmental Disorder Neurons Paired Comparison Parents Pattern Pharmaceutical Preparations Physiological Plastics Population Procedures Proteins Proteomics Protocols documentation Reaction Research Resolution Screening procedure Sensory Signal Transduction Signaling Protein Site Somatosensory Cortex Synapses Synaptic plasticity Testing Tissues Tracer Transgenic Mice Transgenic Organisms Vertebral column Vibrissae Work barrel cortex base classical conditioning conditioning deprivation design experience gamma-Aminobutyric Acid imaging modality improved long term memory molecular marker mouse development neocortical neural circuit novel postsynaptic presynaptic prevent receptor reconstruction research study scaffold sensory system tomography tool

项目摘要

DESCRIPTION (provided by applicant): Synaptic plasticity in many different forms is widely recognized as essential to normal brain development, to homeostasis of the mature brain, and to our abilities to adapt to changing environments and injury and to learn. There is relatively little information, however, to link particular known forms of synaptic plasticity to particular forms or sites of behaviorally relevant brain circuit plasticity. This gap in our knowledge prevents us from efficiently pinpointing synapses of known functional relevance as we explore the molecular, synaptic, and circuit bases of memory and its disorders. The experiments proposed here will exploit unique advantages of the mouse whisker sensory system to explore basic mechanisms of neocortical synaptic plasticity. The work will apply a powerful new high-resolution proteomic imaging method called "array tomography" (AT) to measure molecular and structural characteristics of cortical synapse populations at the level of individual synapses. AT has unique abilities to resolve individual synapses in native circuit tissue context, to measure dozens of distinctive molecular markers (e.g., diverse receptor, transporter, signaling, scaffolding and adhesion proteins) at each synapse, and to do so with very high experimental throughput. Thus, AT can determine a high dimensional molecular signature for each individual synapse in very large populations and differentiate specific synapse subpopulations on the basis of such molecular signatures. The proposed research will develop and apply a novel AT-based screening strategy to search in an unbiased fashion for patterns of structural and molecular change occurring in specific mouse neocortical synapses in reaction to specific sensory adaptation and associative conditioning procedures.

描述（由申请人提供）：以许多不同形式的突触可塑性被广泛认为是正常脑发育，对成熟大脑的体内平衡以及我们适应不断变化的环境和伤害和学习的能力。但是，很少有信息将特定已知形式的突触可塑性形式与行为相关的脑电路可塑性的特定形式或位点联系起来。当我们探索记忆及其疾病的分子，突触和电路基础时，我们的知识差距使我们无法有效地指出已知功能相关性的突触。这里提出的实验将利用小鼠晶须感觉系统的独特优势来探索新皮质突触可塑性的基本机制。这项工作将采用称为“阵列层析成像”（AT）的强大新的高分辨率蛋白质组学成像方法，以测量单个突触水平上皮质突触群体的分子和结构特征。 AT具有独特的能力，可以在每个突触中测量数十个独特的分子标记物（例如，多样的受体，转运蛋白，信号传导，脚手架和粘附蛋白），并在非常高的实验性吞吐量下进行此操作，以测量数十种独特的分子标记物（例如，多样化的受体，转运蛋白，信号传导，脚手架和粘附蛋白）。因此，在非常大的人群中，AT可以确定每个单个突触的高维分子特征，并根据这种分子特征区分特定的突触亚群。拟议的研究将开发并应用基于基于筛查的新颖策略，以公正的方式搜索结构和分子变化的模式在特定的小鼠新皮质突触中发生，以反应特定的感觉适应和关联调节程序。