Pcdhgs pattern starburst amacrine dendrites and direction selective circuits

描述（由申请人提供）：神经元细胞体和过程的规律性是神经系统最显著的特征之一，对认知功能至关重要。这项计划的目的是了解中枢神经系统中神经元树突模式的发展和功能。哺乳动物视网膜是研究神经发育的极好系统，这是由于其规律性、确定的细胞类型以及呈现相关刺激（即图案化光）的能力。 本研究的重点是探讨视网膜星状无长突细胞（SAC）树突和方向选择性视网膜回路的模式。SAC至关重要 用于视网膜神经节细胞的方向选择性视网膜计算，该结构的输出到更高的大脑中心。SAC的定型树突形态及其与方向选择性神经节细胞的精确连接被认为对方向选择性视网膜回路的功能至关重要，但这种树突图案化的机制及其中断的功能后果尚未被测试。如果没有粘附分子的γ-原钙粘蛋白（Pcdhg）家族，SAC就失去了正确排列树突的能力。SAC树突通常从细胞体放射状地生长出来，彼此避免而不避免该区域中的其他SAC;然而，没有Pcdhgs，单个SAC的树突交叉并彼此成束。该提议的目的是（1）理解Pcdhgs的表达如何成为SAC树突图案化的基础，（2）确定SAC树突图案化的发育进展，以及（3）理解径向对称的SAC树突乔木对于视网膜神经节细胞的方向选择性计算的作用。第一个目标将通过Pcdhgs在个体SAC中的表达谱来解决。第二个目标将通过视网膜外植体中SAC树突发育的成像来实现。第三个目标将使用电生理学进行，同时向急性视网膜准备提供视觉刺激。 了解神经回路发育的不同方面至关重要 来了解不同的神经系统紊乱是如何发生作用的。许多神经系统疾病被认为是神经元之间的连接障碍，因此研究神经元如何正常地做出关于连接的决定将有助于科学界更好地理解在病理情况下观察到的微妙变化。 公共卫生相关性：单个神经元之间的正确连接对大脑功能至关重要。理解大脑用来建立这些连接的逻辑将有助于科学界理解在病理情况下，当连接不正确时会发生什么。希望这些研究将有助于治疗大脑发育障碍，并提高公众的生活质量。

DESCRIPTION (provided by applicant): The regularity of neuronal cell bodies and processes is one of the most striking features of the nervous system and is crucial for cognitive function. The aim of this proposal is to understand the development and function of dendritic pattering of neurons in the central nervous system. The mammalian retina is an excellent system for the study of neural development due to its regularity, defined cell types, and the ability to present i with relevant stimuli, that is patterned light. The focus of this study is on the patterning of reinal starburst amacrine cell (SAC) dendrites and direction- selective retinal circuits. SACs are crucial for direction-selective retinal computations by retinal ganglion cells, the structure's output to higher brain centers. The stereotyped dendritic morphology of SACs and their precise connectivity to direction-selective ganglion cells are thought to be crucial for the function of direction-selective retinal circuits, but the mechanism of this dendritic patterning and the functional consequences of its disruption have not been tested direction. Without the gamma-protocadherin (Pcdhg) family of adhesion molecules, SACs lose the ability to pattern their dendrites properly. SAC dendrites normally grow out radially from the cell body avoiding each other without avoiding other SACs in the area; however, without Pcdhgs, the dendrites of an individual SAC cross over and fasciculate with each other. The aims of this proposal are to (1) understand how the expression of Pcdhgs underlies SAC dendritic patterning, (2) determine the developmental progression of SAC dendritic patterning, and (3) understand the role of radially symmetric SAC dendritic arbor for computation of direction-selectivity by retinal ganglion cells. The first aim will be addressed by expression profiling of Pcdhgs in individual SACs. The second aim will be accomplished by imaging of SAC dendrite development in retinal explants. The third aim will be carried out using electrophysiology while presenting visual stimuli to acute retinal preparations. Understanding the different aspects of neural circuit development is crucial for understanding how different disorders of the nervous system take effect. Many disorders of the nervous system are thought to be disorders of connectivity between neurons, so studying how neurons make decisions about connectivity normally will help the scientific community better understand the subtle changes that are observed in pathological situations. PUBLIC HEALTH RELEVANCE: The proper connections made between individual neurons are essential for brain function. Understanding the logic that the brain uses to make these connections will help the scientific community understand what happens in pathological situations, when connections are made incorrectly. Hopefully, these studies will help in the treatment of developmental brain disorders and improve the quality of life for the public.