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.

为了使大脑检测有关外界的相关信号，神经元必须能够收集，操纵 并传输信息。检测运动是视觉系统和专业方向的基本任务 选择性（DS）细胞已经存在于视网膜上。由于其实验可访问性，DS电路 哺乳动物视网膜成为大脑中复杂信息处理的经典模型系统。 视网膜DS神经节细胞通过沿其首选方向运动和输出指南最大程度地激活 反思行为，可能有意识的感知。 现在已经很好地确定，神经节细胞的定向调节反映了starburst amacrine的DS输入 细胞（SAC），其中第一个基本运动检测的步骤发生。 SAC树突从双极细胞转变为DS输出，这表现为在外部运动中更强的运动输出 方向。丰富的文献表明，单个囊中的DS取决于复杂的因素组合， 包括树突形态，突触输入的动力学和电压门控通道的分布。 尽管已经提出了许多不同的机制来解释视觉的转化 从非选择性输入到方向选择性输出的信息，这些过程的相对贡献 对于细胞的功能，仍然存在争议。此外，包含的详细数值模拟 SAC中DS的主要模型低估了实验记录的运动歧视能力 这些细胞表明存在其他未识别的DS机制。 该提案的目的是解决介导单个囊中DS的机制。我们将接受 结合生物物理现实的建模，电生理学以及谷氨酸的创新方法 和钙成像以提供DS中视觉信息表示形式的详细描述 电路，特别关注囊状树突。提出的实验和理论处理将 研究如何将视觉信号转换为神经囊和测试新机制的突触输入 这取决于突触后门控通道以锐化囊树突中的DS信号。 拟议的研究将大大提高我们对视觉系统中DS机制的理解。它 还将为活动通道在树突计算中的参与提供概念上的新作用。