Retinal circuits for precise signaling

用于精确信号传递的视网膜电路

基本信息

批准号：
8755896
负责人：
Robert G Smith
金额：
$ 24万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-09-30 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8755896
关键词：
Advanced Development Amacrine Cells Back Bayesian Analysis Biophysical Process Blindness Brain Calcium Cells Code Complex Computer Simulation Cone Coupling Critical Pathways Data Dendrites Devices Disease Eye Eye diseases Feedback Genetic Glutamates Goals Knowledge Laboratories Lateral Lead Measures Mediating Modeling Morphology Neurons Noise Ocular Prosthesis Pathway interactions Photons Photoreceptors Potassium Channel Process Prosthesis Publishing Research Retina Retinal Role Sensory Shapes Signal Transduction Sodium Channel Stimulus Synapses System Testing Time Varicosity Vertebrate Photoreceptors Vesicle Vision Visual Visual Pathways base grasp improved large-conductance calcium-activated potassium channels luminance neural circuit neurophysiology novel postsynaptic presynaptic public health relevance receptive field response retinal rods ribbon synapse signal processing voltage voltage clamp

项目摘要

DESCRIPTION (provided by applicant): In this application, an expert in the function of retinal circuitry proposes to investigate mechanisms of signal processing and adaptation within the rod pathway for night vision in the mammalian retina. Rod and cone bipolar cells are essential for night and day vision because they transmit and signals from photoreceptors in the outer retina for processing to the inner retina. Understanding how the rod pathway encodes information is a fundamental problem that applies to all sensory pathways, including cone bipolar pathways and cortical circuits. The rod bipolar makes a synaptic ribbon contact onto the A17 amacrine cell, which then makes a reciprocal inhibitory feedback contact onto the rod bipolar cell. Over the past decade, this synaptic connection has been studied by many laboratories, producing a wealth of biophysical details relevant to its function. However, the neurophysiological detail appears so complex that its functional role is difficult to grasp. Recent studies have discovered several mechanisms in the rod bipolar ribbon synapse that cause it to adapt to the background level and to contrast. However the feedback inhibition from the A17 amacrine cell is not thought to contribute to this adaptation. Several other signal processing mechanisms in the A17 have been identified that regulate its feedback. These mechanisms are fundamental and significant because they are similar to those found in many other neurons in the brain. We hypothesize that at night, a divisive receptive field surround from the A17 amacrine cell regulates synaptic release by the rod bipolar cell to improve its signal quality, and that the A17 regulates the laterl extent of the surround according to the background level. We propose to study the effect of amacrine feedback on the synaptic processing performed by the rod and cone bipolar cells. Using realistic computational models of retinal circuitry, we will delineate the possible roles of feedback and feedforward mechanisms involved at the rod bipolar - A17 reciprocal synapse. In Aim 1, we will develop a detailed model of the presynaptic and postsynaptic biophysical mechanisms excluding the details of morphology. We will examine how the known mechanisms for modulating vesicle release by the rod bipolar ribbon can limit or enhance the information content of its signal. Aim 2 will test the hypothesis that negative feedback to the rod bipolar cel generates a divisive spatial surround that enhances the contrast response to twilight signals. In this aim, we will take the model of feedback from Aim 1 and add details of the fine radiating dendrites of the A17 amacrine, including its voltage-gated sodium and potassium channels. Overall, the proposed research will improve our understanding of the signal processing at different background levels performed by visual pathways of the retina. As the rod and cone pathways are critical for vision, the research will improve our understanding of a range of eye diseases. Because these pathways are critical targets for stimulation by visual prostheses and genetic approaches to restoring vision loss from a range of eye diseases, the knowledge gained here will help to advance the development of such devices and treatments.

描述（由申请人提供）：在本申请中，视网膜电路功能的专家建议研究哺乳动物视网膜中夜间视觉的信号处理和适应机制。杆和锥双极细胞对于夜间视觉至关重要，因为它们从视网膜中的光感受器传输并信号以处理内部视网膜。了解杆途径如何编码信息是一个基本问题，它适用于所有感觉途径，包括锥双极途径和皮层电路。杆双极将突触色带接触到A17无花细胞，然后在杆双极细胞上进行相互抑制的反馈接触。在过去的十年中，许多实验室已经研究了这种突触连接，从而产生了与其功能相关的大量生物物理细节。但是，神经生理细节看起来如此复杂，以至于其功能作用难以掌握。最近的研究发现了杆双极色带突触中的几种机制，使其适应背景水平并形成对比。但是，A17无氨酸细胞的反馈抑制不被认为有助于这种适应。 A17中的其他几种信号处理机制已被确定，可以调节其反馈。这些机制是基本的且重要的，因为它们与大脑中许多其他神经元中发现的机制相似。我们假设在夜间，A17无氨基细胞环绕的分裂接收场调节杆双极细胞的突触释放以提高其信号质量，并且A17根据背景水平调节周围的后期范围。我们建议研究杆和锥双极细胞进行的无长链氨酸反馈对突触加工的影响。使用视网膜电路的现实计算模型，我们将描述杆双极性 - A17相互突触中涉及的反馈和前馈机制的可能作用。在AIM 1中，我们将开发出不包括形态学细节的突触前和突触后生物物理机制的详细模型。我们将研究如何通过杆双极色带调节囊泡释放的已知机制可以限制或增强其信号的信息含量。 AIM 2将检验以下假设：对杆双极CEL的负反馈会产生分裂的空间周围，从而增强了对暮光信号的对比反应。在此目标中，我们将从AIM 1中采用反馈模型，并添加A17氨基氨酸的精细辐射树突的细节，包括其电压门控钠和钾通道。总体而言，拟议的研究将提高我们对视网膜视觉途径执行的不同背景水平的信号处理的理解。由于杆和锥形途径对于视觉至关重要，因此该研究将提高我们对各种眼部疾病的理解。由于这些途径是视觉假体刺激的关键目标和恢复各种眼病视力丧失的遗传方法，因此这里获得的知识将有助于推动这种设备和治疗的发展。