Clonal origin of visual cortical microcircuitry

视觉皮层微电路的克隆起源

基本信息

批准号：
8925887
负责人：
Yang DAN
金额：
$ 38.47万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8925887
关键词：
Address Adult Age Amblyopia Animals Area Autistic Disorder Brain Brain Diseases Cells Coupling Dependence Development Exhibits Eye Gap Junctions Glutamates Grant Health Image Knock-out Label Link Literature Maps Measures Mental disorders Molecular Mus N-Methyl-D-Aspartate Receptors NR1 NMDA receptor Neocortex Neurons Neurosciences Potassium Channel Prevention Principal Investigator Process Property Radial Reporting Retroviridae Role Schizophrenia Shapes Sister Speed Stem cells Strabismus Structure Synapses System Techniques Testing Therapeutic Time V1 neuron Visual Visual Cortex Visual impairment Yang area striata base cognitive function dark rearing developmental disease experience insight knock-down nervous system disorder network architecture neurogenesis postnatal programs receptor expression recombinant viral vector research study response two-photon

项目摘要

DESCRIPTION (provided by applicant): The mammalian neocortex is instrumental in a variety of cognitive functions, and understanding cortical circuitry is essential for prevention and treatment of mental disorders. A prominent feature of the cortex is that neurons with similar functional properties are organized in columns. However, how the columnar structure arises during development remains poorly understood. Our recent study in mouse visual cortex has shown that sister neurons originating from a common progenitor cell during early brain development exhibit strong similarity in orientation tuning, arguably the most important functional property in the primary visual cortex. This finding demonstrated, for the first time, a direct correspondence between the ontogenetic and functional columns, and it opened new avenues for studying cortical circuitry. The proposed study aims to address several basic questions concerning the developmental origin of cortical microcircuits, using a combination of techniques including two-photon imaging, electrophysiological recording, neuronal labeling, and molecular perturbation with recombinant viral vectors. By testing whether and how the functional similarity between sister neurons depends on their lineage and physical distances, we will define the basic processing unit of the cortex (Aim 1). By manipulating the excitability and NMDA receptor expression in selected neurons and visual experience of the animal, we will elucidate the interactions between developmental lineage, electrical activity, and visual experience in shaping the functional properties of cortical neurons (Aims 2 and 3). Finally, using high-speed circuit mapping with glutamate uncaging, we will detect common inputs to clonally related sister neurons in order to understand the synaptic basis for their functional similarity. These experiments represent a major step to bridge developmental and systems neuroscience, and they are likely to provide unprecedented insights into the development and organizational principle of cortical microcircuits.

描述（由申请人提供）：哺乳动物新皮质在多种认知功能中发挥着重要作用，了解皮质回路对于预防和治疗精神障碍至关重要。皮层的一个显着特征是具有相似功能特性的神经元按列组织。然而，人们对柱状结构在发育过程中是如何产生的仍然知之甚少。我们最近对小鼠视觉皮层的研究表明，早期大脑发育过程中源自共同祖细胞的姐妹神经元在方向调整方面表现出很强的相似性，这可以说是初级视觉皮层中最重要的功能特性。这一发现首次证明了个体发生和功能柱之间的直接对应关系，并为研究皮层回路开辟了新的途径。拟议的研究旨在结合使用双光子成像、电生理记录、神经元标记和重组病毒载体分子扰动等技术，解决有关皮质微电路发育起源的几个基本问题。通过测试姐妹神经元之间的功能相似性是否以及如何取决于它们的谱系和物理距离，我们将定义皮层的基本处理单元（目标 1）。通过操纵选定神经元的兴奋性和 NMDA 受体表达以及动物的视觉体验，我们将阐明发育谱系、电活动和视觉体验之间在塑造皮质神经元功能特性方面的相互作用（目标 2 和 3）。最后，使用谷氨酸解禁的高速电路映射，我们将检测克隆相关姐妹神经元的共同输入，以了解它们功能相似性的突触基础。这些实验代表了连接发育和系统神经科学的重要一步，它们很可能为皮质微电路的发育和组织原理提供前所未有的见解。