Synaptic Transmission in The Rod Pathway of the Mammalian Retina

项目总结：我们研究计划的主要目标是了解神经回路是如何工作的 取决于组成细胞和突触的固有属性。这项提议的具体目标是 确定视网膜内环路的突触抑制如何影响视网膜神经节的反应 细胞(GC)，视网膜输出通道。 这一提议的重点是对视网膜内回路的抑制：视杆双极(Rb)细胞 小鼠视网膜的通路，由两个中枢神经元组成，即On Rb和AII无长突细胞 (Ac)。AII将RB信号分配到几个视网膜输出通道，最显著的是在α和 在过去的项目期间，我们发现了两个新的α-1和δ-4 对Rb-AII网络提供突触抑制。这两个AC都从锥体上的类型6接收输入 双极(CB)电池，以及6型CB的特性被认为产生对比度敏感性和 OnαGC具有良好的非线性感受场特性。因此，我们提出了这样的假设 视觉场景中的局部对比度最佳地参与了这些新的抑制电路，并且反应 在α和AIIs及其下游的反应中，nNOS-1和Rpb4AC的特性应该是明显的 关闭δGCs。我们的目标是阐明细胞特性和对不同生理刺激的反应 RB通路的各个阶段，以了解这些新的视网膜内回路的功能。这两个具体的 提出的目标将产生对视觉场景的变化如何调制信号编码的理解 在单个视网膜输出通道内：AIM 1测试了nNOS-1 ACS表现出非经典的 感受野周围，表现在视网膜回路下游神经元的反应中；目的 2扩展了我们的组合解剖学和生理学分析，以解决如何区分抑制回路 融合在GC上，并允许对视觉场景的独特组件进行编码。 与公共健康的相关性：了解视网膜是如何实现视觉刺激编码的 突触为视网膜假体的设计和人类视网膜动物模型的研究提供信息 疾病。拟议的工作阐明了视觉信号处理是如何在三个阶段进行调制的。 视网膜网络和解决国家眼科和眼科计划中视网膜疾病计划的两个目标 视觉研究：首先，它建立在从视网膜神经科学获得的知识基础上，以了解视网膜是如何 网络处理视觉图像，第二，它致力于识别光感受器后神经 适应的组成部分。

Project Summary: The broad goal of our research program is to understand how neural circuit function depends on the intrinsic properties of component cells and synapses. The specific goal of this proposal is to determine how synaptic inhibition in inner-retinal circuits shapes responses observed in retinal ganglion cells (GCs), the retinal output channels. This proposal is focused on inhibition in a well-studied inner-retinal circuit: the rod bipolar (RB) cell pathway of the mouse retina, which comprises two central neurons, the ON RB and the AII amacrine cell (AC). The AII distributes the RB signal to several retinal output channels, most significantly the ON α and OFF α and δ GCs, and in the past project period, we identified two novel ACs (nNOS-1 and Rpb4) that provide synaptic inhibition to the RB-AII network. Both of these ACs receive input from the type 6 ON cone bipolar (CB) cell, and the properties of the type 6 CB are thought to generate the contrast-sensitivity and well-characterized nonlinear receptive field of the ON α GC. Therefore, we advance the hypothesis that local contrast in the visual scene best engages these novel inhibitory circuits and that the response properties of nNOS-1 and Rpb4 ACs should be evident in the responses of AIIs and downstream ON α and OFF δ GCs. Our goal is to elucidate cellular properties and responses to physiological stimuli at various stages in the RB pathway to understand the functions of these novel inner retinal circuits. The two specific aims proposed will generate an understanding of how variations in the visual scene modulate signal coding within individual retinal output channels: Aim 1 tests the hypothesis that nNOS-1 ACs exhibit a non-classical receptive field surround that is manifested in the responses of downstream neurons in the retinal circuit; Aim 2 expands our combined anatomical and physiological analyses to resolve how distinct inhibitory circuits converge on GCs and permit coding of unique components of the visual scene. Relevance to Public Health: Understanding how visual stimulus coding is implemented by retinal synapses informs the design of retinal prosthetics and the study of animal models of human retinal diseases. The proposed work clarifies how visual signal processing is modulated at three stages in the retinal network and addresses two goals of the Retinal Diseases Program in the National Plan for Eye and Vision Research: one, it builds on knowledge gained from retinal neuroscience to understand how retinal networks process visual images, and two, it works toward identifying the post photoreceptor neural components of adaptation.