Clonal origin of visual cortical microcircuitry

视觉皮层微电路的克隆起源

• 批准号: 8758789
• 负责人: Yang DAN
• 金额: $ 39.15万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 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/8758789
• 关键词: Address; Adult; Age; Amblyopia; Animals; Area; Autistic Disorder; Brain; Brain Diseases; Cells; Coupling; Dependence; Development; Exhibits; Eye; Gap Junctions; Glutamates; Grant; 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; public health relevance; receptor expression; recombinant viral vector; research study; response; two-photon

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）：哺乳动物新皮层在多种认知功能中发挥了作用，理解皮质回路对于预防和治疗精神障碍至关重要。皮层的一个突出特征是在列中组织了具有相似功能特性的神经元。但是，在开发过程中出现柱状结构的理解仍然很少。我们最近在小鼠视觉皮层的研究表明，早期大脑发育过程中源自公共祖细胞的姐妹神经元在方向调节中表现出很强的相似性，这可以说是主要视觉皮层中最重要的功能性能。这一发现首次证明了个体遗传学和功能柱之间的直接对应关系，并为研究皮质回路开辟了新的途径。拟议的研究旨在解决有关皮质微电路发育起源的几个基本问​​题，其中包括两种技术的组合，包括两光子成像，电生理记录，神经元标记和分子扰动与重组病毒载体。通过测试姐妹神经元之间的功能相似性以及如何取决于其谱系和物理距离，我们将定义皮质的基本处理单元（AIM 1）。通过操纵所选神经元中的兴奋性和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时的相互作用（AIMS 2和3）。最后，使用高速电路映射与谷氨酸未成仪，我们将检测到与克隆相关的姐妹神经元的共同输入，以了解其功能相似性的突触基础。这些实验代表了桥接发育和系统神经科学的主要步骤，它们可能会对皮质微电路的发展和组织原理提供前所未有的见解。