Functional roles of electrical synapses formed by neuronal gap junctions

间隙连接是由连接蛋白形成的细胞间通讯通道的聚集体，连接蛋白在整个身体的细胞中具有重要作用。当神经元之间发生缝隙连接时，它们产生电突触，介导神经元之间的直接电通信。纳吉的研究小组和其他人已经揭示了电突触在哺乳动物大脑和脊髓的许多区域中的普遍性和重要性。他的研究计划集中在两个长期目标：i）破译电突触的结构和调节蛋白质成分; ii）获得这些突触在神经元电路中的功能作用的知识。后一个目标的拟议工作的目的是提供基本的了解电突触的发生和要求在三个不同的神经元系统，其中每一个从根本上管理重要的生理过程。他们假设，电突触赋予新的功能特性，并有助于基本的同步机制，这是关键的神经元活动在这些系统中的每一个和这些系统的功能subserve。 要检查的三个系统包括：i）初级传入无髓鞘感觉C纤维，其具有许多重要功能，包括生理学上关键的外周轴突反射的介导。据报道，这些纤维在几十年前被电耦合，但这种耦合的基础仍然未知。Nagy最近发现了感觉神经元中存在差距连接形成蛋白connexin 36的证据，并旨在确定Cx 36介导感觉纤维之间的电耦合，这将从根本上改变对轴突反射机制基础的理解; ii）脊髓中的性二态运动神经元，控制膀胱排空和性活动，Nagy的研究小组最近在那里发现了大量由连接蛋白形成的电突触36;和iii）脊髓中的节前交感神经元，已知在那里发生电突触，但对这些突触的组织或它们的功能作用一无所知，对于更完整地理解交感神经元如何控制自主功能的主体来说，需要了解这些知识。 Nagy将在正常小鼠中使用生物化学，解剖学和超微结构方法来确定电突触发生的部位，并在转基因小鼠中使用生理学策略来确定这些突触如何有助于待检查系统的操作。结果将增加新的知识，这些突触在神经元回路中发挥的复杂和关键作用，并将作为翻译的关键机械概念周围的电突触在维持整个器官的生理运作的重要性。

Gap junctions are aggregates of intercellular communication channels formed by connexin proteins that have essential roles in cells throughout the body. When gap junctions occur between neurons, they create electrical synapses that mediate direct electrical communication between neurons. Nagy’s group and others have revealed both the prevalence and importance of electrical synapses in many regions of mammalian brain and spinal cord. His research program is centered on two long-term objectives: i) deciphering the structural and regulatory protein components of electrical synapses; and ii) gaining knowledge of the functional roles of these synapses in neuronal circuitry. Proposed work on the latter objective aims to provide basic understanding of the occurrence and requirements for electrical synapses in three different neuronal systems each of which govern fundamentally important physiological processes. They hypothesize that electrical synapses confer novel functional properties and contribute essential synchronizing mechanisms that are key to neuronal activity in each of these systems and the functions these systems subserve. The three systems to be examined include: i) Primary afferent unmyelinated sensory C-fibers that have many important functions, including mediation of the physiologically critical peripheral axon reflex. These fibers were reported to be electrically coupled decades ago, but the basis for this coupling remains unknown. Nagy recently found evidence for the presence of the gap junction forming protein connexin36 in sensory neurons, and aims to establish that Cx36 mediates electrical coupling between sensory fibers, which would fundamentally shift understanding of the mechanistic basis of the axon reflex; ii) Sexually dimorphic motoneurons in spinal cord, which control bladder emptying and sexual activity and where Nagy’s group recently found an abundance of electrical synapses formed by connexin36; and iii) Preganglionic sympathetic neurons in the spinal cord, where electrical synapses are known to occur, but nothing is known about the organization of these synapses or of their functional role, knowledge of which is required for a more complete understanding of how sympathetic neurons control a host of autonomic functions. Nagy will use biochemical, anatomical and ultrastructural approaches in normal mice to identify sites where electrical synapses occur and physiological strategies in transgenic mice to establish how these synapses contribute to the operation of the systems to be examined. Results will add to emerging knowledge of the novel, intricate and critical roles these synapses play in neuronal circuitry, and will serve as translation of key mechanistic concepts surrounding electrical synapses to their importance in maintaining operations of whole organ physiology.