Transient Mixed Synapses Regulate Emerging Connectivity in Simple Neuronal Networks



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The electrical synapse was first described over 50 years ago. Since that time appreciation of its complexity and importance has grown, including the hypothesis that early transient formation of these synapses is important to adult patterns of connectivity in neural networks. Presented in this dissertation are studies utilizing identified neurons in cell culture from the snail Helisoma trivolvis to examine discrete periods of electrical synapse formation during regeneration with sustained or transient expression. Extensive knowledge of connectivity patterns of the buccal neurons of Helisoma in cell culture and the ganglia, provide a useful framework for looking at modulation and manipulation of electrical synapses and their impact and emerging connectivity in a simple neuronal network. Two types of electrical connections were observed those that were transient, between a B19 and a B110 and those that were sustained, between a B19 and another B19. Dopamine (DA) modulation of forming electrical synapses (FES) produces a synapse specific effect at those either destined to be transient (TES) or sustained (SES) and may be a direct effect on the gap junctions at the synapses, as is the case at TES, or an indirect effect on other membrane currents, as seen in SES. DA modulation produces different outcomes at SES-centered networks and TES-centered networks with respect to new chemical synapse formation, demonstrating network-dependent effects of electrical synapse modulation. Pharmacological blockade of chemical and electrical components at forming mixed synapses in some cases alters subsequent synapse formation although due to the variable nature does not appear to be a direct interaction between chemical and electrical synapses. Three-cell networks appear to display a balancing mechanism for overall electrical coupling when electrical synapses are blocked suggesting a competition for some resource in the construction or trafficking of gap junctions. In addition to electrophysiological examinations, network coupling can be assessed utilizing fluorescent calcium imaging to look at coincidence of calcium changes as an output for coupling between cells. This technique provides a useful tool for less invasive studies of neuronal networks and the impact of coupling at mixed synapses.