Mechanisms of Motion Detection in Retinal Neural Network

视网膜神经网络运动检测机制

• 批准号: 10164792
• 负责人: Tomomi Ichinose
• 金额: $ 48.47万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10164792
• 关键词: Acetylcholine; Agonist; Biological; Bungarotoxins; Cells; Cholinergic Receptors; Code; Color; Data; Dendrites; Detection; Distal; Exhibits; Goals; Image; Immunohistochemistry; Individual; Knowledge; Light; Measures; Modeling; Molecular; Morphology; Motion; Mus; Neural Retina; Neurons; Neurophysiology - biologic function; Play; Process; Property; Reflex action; Research Project Grants; Retina; Role; Signal Transduction; Synapses; Testing; Transgenic Mice; Visual; Visual Motion; Visual system structure; alpha-bungarotoxin receptor; cell type; gamma-Aminobutyric Acid; ganglion cell; neural circuit; neural correlate; neural network; neuromechanism; patch clamp; receptor; response; starburst amacrine cell; transmission process

The long term goal of this research project is to elucidate the functions of neural network in the retina. A key function of the retina is to encode distinct components of the image world, such as color and motion, by multiple neural networks. Direction selective ganglion cells (DSGCs) play a major role in motion detection because they respond to an object as it moves in a particular direction. Starburst amacrine cells (SACs) contribute to direction selectivity in DSGCs by releasing GABA onto a DSGC only when an object moves from its proximal to distal dendrites, but not when an object moves in the opposite direction, resulting in unidirectional DSGC excitation. While the classic Barlow-Levick model remains the fundamental explanation of direction selectivity, this model does not explain acetylcholine release from SACs and heterologous synaptic connections between bipolar cells and SACs. Using patch clamp recordings together with morphological and molecular biological approaches, we have investigated the temporal properties of individual bipolar and ganglion cells and correlated neural circuits coding components of the image world. We recently found that type 2 and 7 bipolar cells express bungarotoxin-sensitive, α7 acetylcholine receptors (α7AChRs) and depolarize in response to a puff application of a α7AChR agonist. Because these bipolar cells provide synaptic inputs to SACs at their proximal dendrites, we propose a new model of direction selectivity: when an object moves from proximal to distal dendrites of SACs, the type 2 and 7 bipolar cells are activated through α7AChR signaling and boost the excitation in SACs (preferred direction for SACs). In contrast, activation of these bipolar cells is delayed by an object moving in the opposite direction, which in turn provides less excitation to SACs (null direction for SACs). We will explore this model as follows: we will investigate the types of bipolar cells that express α7AChRs using immunohistochemistry and patch clamp recordings (Aim 1). Then, we will generate a transgenic mouse in which α7AChRs are eliminated from bipolar cells. Using this mouse, we will test whether the direction selectivity of SACs is reduced (Aim 2). Finally, we will test whether the direction selectivity of downstream neurons is reduced by α7AChRs elimination from bipolar cells (Aim 3). The results of this study will increase our understanding of neural mechanisms of motion detection.

这项研究计划的长期目标是阐明视网膜神经网络的功能。一个关键 视网膜的功能是编码图像世界的不同组成部分，如颜色和运动， 多个神经网络方向选择性神经节细胞在运动检测中起着重要作用 因为当物体向特定方向移动时，它们会做出反应。星爆型无长突细胞 通过仅当物体移动时将GABA释放到DSGC上，有助于DSGCs的方向选择性 它的近端到远端树突，但不是当一个物体在相反的方向移动，导致 单向DSGC激励。虽然经典的巴洛-莱维克模型仍然是对 方向选择性，这个模型不能解释从SAC和异源突触释放乙酰胆碱。 双极电池和SAC之间的连接。采用膜片钳记录结合形态学和 分子生物学的方法，我们已经调查了个人的双极和 神经节细胞和相关的神经回路编码图像世界的组成部分。我们最近发现， 2型和7型双极细胞表达银环蛇毒素敏感的α7乙酰胆碱受体（α 7 AChRs）， 响应于α 7 AChR激动剂的喷吹应用的去乙酰化。因为这些双极细胞提供突触 输入到SAC在其近端树突，我们提出了一个新的模型的方向选择性：当一个对象 从近端树突向远端树突移动，通过α 7 AChR激活2型和7型双极细胞 信号并增强SAC中的激发（SAC的首选方向）。相反，激活这些 双极细胞被在相反方向移动的物体延迟，这反过来又提供了较少的兴奋， SAC（空方向SAC）。我们将探讨这个模型如下：我们将调查类型的双极 使用免疫组织化学和膜片钳记录表达α 7 AChRs的细胞（Aim 1）。那就 产生从双极细胞中消除α 7 AChR的转基因小鼠。使用这只鼠标，我们将 测试SAC的方向选择性是否降低（目标2）。最后，我们将测试方向是否 下游神经元的选择性被双极细胞中的α 7 AChR消除而降低（目的3）。的结果 这项研究将增加我们对运动检测的神经机制的理解。