Mechanisms of Motion Detection in Retinal Neural Network

这项研究的长期目标是阐明神经网络在视网膜中的功能。一把钥匙 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，通过 多个神经网络。方向选择性神经节细胞(DSGCs)在运动检测中起重要作用 因为当物体朝特定方向移动时，它们会对物体做出反应。星爆无长突细胞(囊) 仅当对象从以下位置移动时，才将GABA释放到DSGC上，从而有助于DSGCs中的方向选择性 它靠近远端的树突，但当物体向相反方向移动时不会，导致 单向直接脉宽调制励磁。虽然经典的巴洛-列维克模型仍然是对 方向选择性，这个模型不能解释从囊和异源突触释放乙酰胆碱 双极细胞和囊之间的连接。将膜片钳记录与形态和 分子生物学方法，我们研究了个体双相和 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(α7AChRs)和 对α7AChR激动剂的喷雾应用作出去极化反应。因为这些双极细胞提供突触 我们提出了一个新的方向选择性模型：当一个物体 通过α7AChR，2型和7型双极细胞从囊的近端树突移动到远端树突 在囊中传递信号并增强激发(囊的首选方向)。相反，激活这些 双极细胞被向相反方向移动的物体延迟，这反过来又提供更少的兴奋给 SACS(SACS为空方向)。我们将按如下方式探索该模型：我们将研究双极的类型 使用免疫组织化学和膜片钳记录表达α7AChRs的细胞(目标1)。那么，我们会 产生一种转基因小鼠，在其中α7AChR从双极细胞中消除。使用这个鼠标，我们将 测试SACS的方向选择性是否降低(目标2)。最后，我们将测试方向是否 通过从双极细胞中消除α7AChRs，下游神经元的选择性降低(目标3)。结果是 这项研究将加深我们对运动检测的神经机制的理解。

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.