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: 10305620
• 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/10305620
• 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部世界的相关信号，神经元必须能够收集、操纵 并传递信息。检测运动是视觉系统的一项基本任务，也是专门的方向 选择性（DS）细胞已经存在于视网膜中。由于其实验可访问性，DS 电路 哺乳动物的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而被最大程度地激活，并且其输出引导 反射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节反映了来自星爆无长突的 DS 输入 细胞（SAC），运动检测的第一个基本步骤发生在其中。 SAC 树突将来自双极细胞的非 DS 输入转换为 DS 输出，这表现为向外运动的更强输出 方向。丰富的文献表明，单个 SAC 中的 DS 取决于多种因素的复杂组合， 包括树突形态、突触输入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 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 对细胞功能的影响仍存在争议。此外，详细的数值模拟包含 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，表明存在其他未识别的 DS 机制。 该提案的目标是解决在各个 SAC 中调解 DS 的机制。我们将采取 结合生物物理真实建模、电生理学以及谷氨酸的创新方法 和钙成像提供 DS 中视觉信息表示的详细描述 电路，特别关注 SAC 树突。拟议的实验和理论治疗将 研究视觉信号如何转化为神经 SAC 的突触输入并测试一种新机制 这依赖于突触后电压门控通道来锐化 SAC 树突中的 DS 信号。 拟议的研究将极大地增进我们对视觉系统中 DS 机制的理解。它 还将为活跃通道参与树突计算提供概念上新颖的角色。