Role of electrical synapses in vision

化学和电子通信是神经系统中已知的两种传输方式。从历史上看，电传输在20世纪40年代至50年代就已经为人所知，但其功能意义在很大程度上被忽视，并引起了争议性的讨论。今天，人们同意两个不同的通道形成蛋白家族，泛连接蛋白和连接蛋白，参与电通信，但我们不了解这些过程的详细规则和机制。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。我们可以证明外视网膜电传输的一个分子决定因素是连接蛋白。此外，我们证明化学突触和电突触具有相似的分子机制来实现突触可塑性。现在，这些现有的结果让我们通过研究利用钙、ATP和一氧化氮的主要信号通路如何聚集在两种不同的泛联蛋白结构上，从不同的角度来解决电突触的功能。系统的和环境相关的结构-功能分析将为关键的蛋白质结构、通道功能和体外调节回路提供重要的新见解，这些知识的获得适用于合理设计动物模型，以解决神经网络可塑性和体内行为中的通道功能。这些研究将为通过泛内联蛋白将突触传递纳入连接视觉系统功能的主要信号通路的生理上有意义的调节网络奠定基础。

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.