Exploring the role of gap junction-associated proteins in electrical synaptic transmission and its regulation

Abstract

Plasticity of chemical synaptic transmission has been extensively investigated; on the other hand little is known about the plastic properties of gap junction-mediated electrical synapses. Since the finding that electrical transmission can be regulated by activity and neuromodulators at identifiable synapses between auditory afferents and the Mauthner cell lateral dendrite, efforts have been made in trying to understand the functional role of electrical coupling between neurons in the central nervous system, since these findings could constitute a widespread property of electrical synapses in general. However, the functional significance and the intracellular mechanisms underlying junctional conductance and its modulation at these electrical synapses remain poorly understood. Recent work using the goldfish Mauthner cell system has shown that enhancement of electrical coupling at electrical synapses dependent of their nearby chemical synapses, influx of calcium, and the activation of Ca++calmodulin-dependent kinase II (CaM-KII). In the present work I focused on the potential mechanisms underlying electrical transmission and its modulation. I postulated that, like chemical synaptic transmission and its modulation, gap junction-mediated electrical transmission and regulation result from interplay between gap junction channels with multiple scaffolds, such as ZO-1 (Chapter 2), and regulatory proteins, such as CaM-KII (Chapter 3), and that electrical transmission involves exocytic and endocytic events (Chapter 4). Furthermore, we were able to identify a novel tool for Mauthner cell identification which further advances our ability to study this model system (Chapter 5).