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.

Durante o desenvolvimento pós-natal do hipocampo, as junções comunicantes (JC) formadas por conexinas (Cxs) neuronais participam na maturação da circuitaria hipocampal promovendo a regulação da atividade espontânea sincronizada neuronal. Neste estudo investigamos as duas Cxs neuronais mais abundantes no hipocampo, a Cx36 e Cx45, durante o desenvolvimento pós-natal. Identificamos mudanças nos níveis de transcritos e proteicos da Cx36 e Cx45 ao longo deste período. Nossos resultados revelaram que ambas as Cxs neuronais estão presentes nas sub-regiões do hipocampo e que sua distribuição é modulada em função da progressão do desenvolvimento. Atráves da avaliação dos níveis de atividade neuronal identificamos diferenças exercidas pelo bloqueio das JCs em hipocampo de neonatos e na segunda semana de vida. Nossos resultados mostram que as Cxs neuronais são reguladas durante o desenvolvimento pós-natal do hipocampo, assim como sua ação sobre sua excitabilidade, mostrando que as Cxs podem contribuir de forma distinta em periodo específicos do desenvolvimento hipocampal. / Gap junctions (GJ) composed of neuronal connexins (Cx) play a significant role in the activity-dependent circuitry maturation promoting modulation of coherent spontaneous neuronal activity. Herein, we evaluate two major hippocampal neuronal Cxs, Cx36 and Cx45 during postnatal development. We identified changes in Cx36 and Cx45 transcript and protein levels during these developmental periods. Interestingly, immunofluorescence analyses showed that Cx36 and Cx45 are located in all hippocampal subregions. Also, neuronal Cx distribution in these sub-regions is modulated throughout postnatal development. Using electrophysiological recording, we identified changes imposed by GJ blocker over the hippocampal activity in neonates and two-week-old rats. Our finds demonstrate a regulation of neuronal Cxs and distinct GJ role in activity modulation during postnatal hippocampal development, which might be essential to physiological processes that govern proper hippocampal development.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal