Mechanisms of direction selectivity in starburst amacrine cells

星爆无长突细胞的方向选择性机制

• 批准号: 10063526
• 负责人: Alon Poleg-Polsky
• 金额: $ 36.63万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10063526
• 关键词: Address; Behavior; Biological Models; Biophysics; Brain; Calcium; Calcium Signaling; Cell physiology; Cells; Complex; Conflict (Psychology); Conscious; Data; Dendrites; Detection; Discrimination; Distal; Electrophysiology (science); Formulation; Generations; Glutamates; Goals; Guidelines; Image; Individual; Investigation; Literature; Measurement; Measures; Mediating; Methodology; Mission; Modeling; Morphology; Motion; Neurons; Output; Perception; Pharmacology; Photic Stimulation; Photoreceptors; Physiological; Population; Potassium Channel; Process; Property; Reflex action; Research; Retina; Role; Shapes; Signal Transduction; Site; Stimulus; Synapses; System; Testing; Time; Visual; Visual Perception; Visual system structure; Work; base; experimental study; ganglion cell; imaging approach; improved; information processing; innovation; neuronal cell body; novel; novel strategies; postsynaptic; predictive test; preference; presynaptic; receptive field; relating to nervous system; response; signal processing; simulation; starburst amacrine cell; visual information; visual processing; voltage gated channel

For the brain to detect relevant signals about the outside world, neurons must be able to collect, manipulate and transmit information. Detecting motion is a fundamental task of the visual system, and specialized direction selective (DS) cells are present already at the retina. Due to its experimental accessibility, the DS circuit in the mammalian retina emerged as a classical model system of a sophisticated information processing in the brain. Retinal DS ganglion cells are maximally activated by motion in their preferred direction, and their output guides reflexive behavior and possibly conscious perception. It is now well established that directional tuning of the ganglion cells reflects DS input from starburst amacrine cells (SAC), where the first fundamental step of motion detection takes place. SAC dendrites transform a non-DS input from bipolar cells into DS output that is manifested as a stronger output for motion in the outward direction. A rich literature indicates that DS in individual SACs depends on an intricate combination of factors, including dendritic morphology, dynamics of the synaptic inputs and the distribution of voltage-gated channels. While a number of different mechanisms have been proposed to explain the transformation of visual information from unselective inputs into direction selective output, the relative contribution of these processes to the function of the cell remains controversial. In addition, detailed numerical simulations that incorporate the leading models of DS in SACs underestimate the experimentally recorded motion discrimination abilities in these cells, indicating the presence of additional unidentified DS mechanism(s). The goal of this proposal is to address the mechanisms that mediate DS in individual SACs. We will take an innovative approach that combines biophysically realistic modeling, electrophysiology, as well as glutamate and calcium imaging to provide a detailed description of the of the visual information representation in the DS circuit, with a particular focus on SAC dendrites. The proposed experimental and theoretical treatment will study how visual signals are transformed to synaptic inputs that innervate SACs and test a novel mechanism that depends on postsynaptic voltage-gated channels to sharpen DS signals in SAC dendrites. The proposed research will substantially advance our understanding of DS mechanisms in the visual system. It will also provide a conceptually novel role for the participation of active channels in dendritic computations.

为了让大脑检测到外界的相关信号，神经元必须能够收集、操纵 并传输信息。运动检测是视觉系统的一项基本任务， 选择性（DS）细胞已经存在于视网膜上。由于其实验可及性， 哺乳动物视网膜是大脑复杂信息处理的经典模型系统。 视网膜DS神经节细胞最大限度地激活运动在他们的首选方向，和他们的输出指南 反射性行为和可能的有意识感知。 现在已经确定，神经节细胞的定向调谐反映了来自星状无长突的DS输入 细胞（SAC），其中发生运动检测的第一个基本步骤。SAC树突将来自双极细胞的非DS输入转换为DS输出，其表现为向外运动的更强输出。 方向大量文献表明，单个SAC中的DS取决于复杂的因素组合， 包括树突形态学、突触输入的动力学和电压门控通道的分布。 虽然已经提出了许多不同的机制来解释视觉的转变， 信息从非选择性输入到方向选择性输出，这些过程的相对贡献 对细胞功能的影响仍然存在争议。此外，详细的数值模拟，包括 SAC中DS的主要模型低估了实验记录的运动辨别能力， 这些细胞，表明存在其他未鉴别的DS机制。 该提案的目标是解决在个体SAC中介导DS的机制。我们将采取一个 创新的方法，结合生物病理学逼真的建模，电生理学，以及谷氨酸 和钙成像，以提供DS中视觉信息表示的详细描述 电路，特别关注SAC树突。建议的实验和理论处理将 研究视觉信号如何转化为神经支配SAC的突触输入，并测试一种新的机制 这取决于突触后电压门控通道来锐化SAC树突中的DS信号。 这项研究将大大促进我们对视觉系统中DS机制的理解。它 也将提供一个概念上的新角色，在树突状计算的积极渠道的参与。