Functional roles of electrical synapses formed by neuronal gap junctions

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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. **