High-Throughput Analysis of Synaptic Diversity and Plasticity in Mouse Barrel Cor

新皮层微电路内连接的可塑性被认为是感知学习和记忆的基础。小鼠须桶皮层具有优越的感觉和运动外周，其柱状结构的明显性和可及性与啮齿类动物和其他哺乳动物的所有其他新皮层区域的结构高度相似，为研究新皮层可塑性提供了许多独特的实验优势。尤其是老鼠，因为它的体积小和越来越强大的遗传学工具的可用性，为成像研究提供了特殊的优势。现在，人们普遍期望，对小鼠桶状皮质可塑性的研究将在未来几年提供最有希望的途径之一，以实现对健康和疾病中新皮质学习和记忆机制的一般细胞和分子理解。

Plasticity of connections within the neocortical microcircuit is thought to be the substrate for perceptual learning and memory. Mouse whisker barrel cortex offers many unique experimental advantages for the study of neocortical plasticity because of an advantageous sensory and motor periphery and because of the obviousness and accessibility of its columnar architecture, which is highly similar to the architecture of all other regions of neocortex in rodents and other mammals. The mouse in particular offers special advantages for imaging studies because of its small size and the availability of increasingly powerful genetics tools. It is now widely expected that work on the plasticity of mouse barrel cortex will provide for the next few years one of the most promising avenues toward a general cellular and molecular understanding of neocortical learning and memory mechanisms in health and disease. Array tomography (ATom) (Micheva and Smith 2007) is a groundbreaking new imaging technique developed by the Smith lab, which for the first time allows high-throughput analysis of the molecular architecture of tissue at the single-synapse level. This capacity for high- throughput single-synapse analysis provides an unprecedented opportunity to measure neocortical synaptic changes on a comprehensive and panoramic scale and at a level of detail and quantitative reliability far beyond previous experimental approaches. We will use high- throughput ATom to explore the modification of the synaptic microcircuitry of the mouse whisker barrel by altered sensory stimulation, identify specific synapse populations most subject to such modification and characterize corresponding changes in synapse protein composition and structure. This unique new perspective on changes in the molecular architectures of individual synapses is expected to provide an extraordinarily valuable complement to in vivo studies of whisker barrel plasticity being carried out in many other laboratories. Specific Aim 1: To define the laminar distributions of distinct synaptic populations within a barrel column and assess the variability of this synaptic architecture between columns and animals. Specific Aim 2: To characterize the effect of long term principal whisker stimulation on the laminar distributions of distinct synapse populations within the barrel column microcircuit. Specific Aim 3: To compare the plasticity of distinct populations of synapses onto layer 4 spiny stellate cells and layer 5 pyramidal cells.