Role of electrical synapses in vision

电突触在视觉中的作用

• 批准号: 418142-2012
• 负责人: Zoidl, Georg
• 金额: $ 2.26万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630585
• 关键词: Role; electrical; synapses; vision

Chemical and electrical communication are the two known types of transmission used in the nervous system. Historically, electrical transmission was already known by the 1940-1950s, but the functional significance largely ignored and controversially discussed. Today, it is agreed that two distinct families of channel forming proteins, the pannexins and connexins, participate in electrical communication, but we don't understand the rules and mechanisms of these processes in detail. It is my goal to demonstrate the physiological relevance of electrical transmission in particular in the visual system from molecules to systems to behavior. Major steps forward were achieved recently. We could prove that one molecular determinant of electrical transmission in the outer retina is a connexin protein. In addition, we demonstrated that chemical and electrical synapses share similar molecular mechanisms to achieve synaptic plasticity. Now, these exiting results let us address the functions of electrical synapses from a different angle by studying how major signaling pathways utilizing calcium, ATP and nitric oxide converge on the structure of two distinct pannexin proteins. A systematic and context dependent structure-function analysis as outlined will provide important novel insight into critical protein structures, channel functions and regulatory circuits in vitro, with the gain in knowledge applicable for rational design of animal models to address channel functions in neuronal network plasticity and behavior in vivo. These studies will form the basis to fit synaptic transmission through pannexins into physiologically meaningful regulatory networks linking major signaling pathways to function(s) of the visual system.

化学和电通信是神经系统中使用的两种已知类型的传输。从历史上看，电力传输在1940- 1950年代就已经为人所知，但其功能意义在很大程度上被忽视，并引起了争议。今天，人们一致认为两个不同的通道形成蛋白家族，pannexins和connexins，参与电通信，但我们不了解这些过程的规则和机制的细节。我的目标是证明电传输的生理相关性，特别是在视觉系统中，从分子到系统再到行为。最近取得了重大进展。我们可以证明，在视网膜外层的电传输的一个分子决定因素是连接蛋白。此外，我们证明了化学和电突触共享相似的分子机制来实现突触可塑性。现在，这些令人兴奋的结果让我们从不同的角度来解决电突触的功能，通过研究利用钙，ATP和一氧化氮的主要信号通路如何聚集在两种不同的泛连接蛋白的结构上。所概述的系统的和上下文相关的结构-功能分析将提供重要的新的洞察关键蛋白质结构，通道功能和体外调控电路，与知识的增益适用于合理设计的动物模型，以解决通道功能在神经网络的可塑性和行为在体内。这些研究将形成基础，以适应突触传递通过pannexins到生理上有意义的调节网络连接的主要信号通路的视觉系统的功能（S）。