Synaptic Transmission in The Rod Pathway of the Mammalian Retina

项目概述：我们研究计划的主要目标是了解神经回路的功能 取决于组成细胞和突触的内在属性。该提案的具体目标是 确定视网膜内回路中的突触抑制如何塑造视网膜神经节中观察到的反应 细胞（GC），视网膜输出通道。 这项建议的重点是抑制在一个充分研究的内部视网膜电路：杆双极（RB）细胞 小鼠视网膜的通路，其包括两个中枢神经元，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，最重要的是ON α和 OFF α和δ GC，在过去的项目期间，我们鉴定了两种新的AC（nNOS-1和Rpb 4）， 提供对RB-AII网络的突触抑制。这两个AC都从类型6 ON锥接收输入 双极（CB）电池，而6型CB的特性被认为产生对比敏感度， ON α GC的良好表征的非线性感受野。因此，我们提出假设， 视觉场景中的局部对比度最好地参与了这些新的抑制回路， nNOS-1和Rpb 4 AC的特性在AIIs和下游ON α的反应中应该是明显的， 关闭δ GC。我们的目标是阐明细胞特性和对不同生理刺激的反应， 阶段的RB途径，以了解这些新的内部视网膜电路的功能。的两个具体 提出的目标将产生对视觉场景中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：目的1测试nNOS-1 AC表现出非经典的视网膜输出通道的假设。 感受野周围，表现在视网膜回路中下游神经元的反应中;目的 2扩展了我们的结合解剖和生理分析，以解决不同的抑制回路 收敛在GC上，并允许编码视觉场景的独特组件。 与公共卫生的相关性：了解视觉刺激编码是如何通过视网膜实现的 突触为视网膜假体的设计和人类视网膜的动物模型的研究提供了信息。 疾病拟议的工作澄清了视觉信号处理是如何调制在三个阶段， 视网膜网络，并解决两个目标的视网膜疾病计划在国家计划的眼睛和 视觉研究：首先，它建立在从视网膜神经科学中获得的知识基础上，以了解视网膜神经系统是如何工作的。 网络处理视觉图像，第二，它致力于识别感光后神经 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.