Pcdhgs pattern starburst amacrine dendrites and direction selective circuits

描述(申请人提供)：神经元胞体和突起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。这一建议的目的是了解中枢神经系统中神经元树突图案的发育和功能。哺乳动物的视网膜是研究神经发育的优秀系统，因为它的规律性，明确的细胞类型，以及向I提供相关刺激的能力，即有图案的光。这项研究的重点是视网膜星状爆裂无长突细胞(SAC)树突和方向选择性视网膜回路的模式。SAC是至关重要的 对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。囊的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，但这种树突模式的机制及其破坏的功能后果尚未被测试方向。如果没有γ-原钙粘附素(Pcdhg)家族的黏附分子，囊泡就失去了正确排列树突的能力。通常情况下，囊状突起从细胞体径向生长，彼此避开彼此，而不避开该区域的其他囊泡；然而，如果没有Pcdhgs，单个囊状突起的树突会彼此交叉并成束状生长。本研究的目的是(1)了解Pcdhgs的表达是如何支持SAC树突状构型的，(2)确定SAC树突状构型的发育进程，以及(3)了解径向对称的SAC树突状突起在计算视网膜神经节细胞的方向选择性中的作用。第一个目标将通过在单个囊泡中表达Pcdhgs来实现。第二个目标将通过对视网膜外植体中SAC树突发育的成像来实现。第三个目标将利用电生理学实现，同时将视觉刺激呈现给急性视网膜准备。了解神经回路发育的不同方面是至关重要的 以了解不同的神经系统紊乱是如何起作用的。许多神经系统疾病被认为是神经元之间连接的障碍，因此研究神经元如何正常做出连接决定将有助于科学界更好地了解在病理情况下观察到的细微变化。 与公共健康相关：单个神经元之间建立的适当联系对大脑功能至关重要。了解大脑用来建立这些联系的逻辑将有助于科学界理解在病理情况下，当联系建立得不正确时会发生什么。希望这些研究将有助于治疗发育性大脑疾病，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.