Role of electrical synapses in vision

化学通信和电子通信是神经系统中使用的两种已知的传输类型。从历史上看，电气传动早在1940-1950年代就已经知道了，但其功能意义在很大程度上被忽视了，并引起了争议。今天，人们已经达成共识，两个不同的通道形成蛋白家族--连接蛋白和连接蛋白--参与了电通讯，但我们并不详细地了解这些过程的规则和机制。我的目标是证明电传递的生理学相关性，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，决定视网膜外层电传递的一个分子决定因素是连接蛋白。此外，我们还证明了化学突触和电突触具有相似的实现突触可塑性的分子机制。现在，这些现有的结果让我们可以从不同的角度研究电突触的功能，研究利用钙、三磷酸腺苷和一氧化氮的主要信号通路如何汇聚在两个不同的pAnnin蛋白的结构上。系统的和上下文相关的结构-功能分析将为体外关键蛋白质结构、通道功能和调节电路提供重要的新见解，并为合理设计动物模型以解决体内神经网络可塑性和行为中的通道功能提供适用的知识。这些研究将形成基础，使突触传递通过膜联蛋白进入具有生理意义的调节网络，将主要信号通路连接到视觉系统的功能(S)。

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.