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.

Light entering the eye is transformed by the retina into electrical signals. Extensive processing takes place in the retina before these signals are transmitted to the brain. Beginning in the outer retina, light-evoked electrical signals are distributed into parallel pathways specialized for different visual tasks, such as the detection of dark vs. bright ambient light, the onset or offset of light, and the direction of stimulus motion. Pathway diversity is a consequence of cell type diversity, differential cell connectivity, synapse organization, receptor expression, or any combination thereof. Cell connectivity itself can be accomplished through excitatory or inhibitory chemical synapses, or electrical coupling via gap junctions. Gap junctions are further specialized based on the expression of different connexin subunit isoforms. In aggregate, this diversity gives rise to ganglion cells with highly specialized functions, including ON and/or OFF responses, contrast-tuning and direction-selectivity (DS). The directionally-selective circuit, a circuit specialized for the encoding of stimulus motion, makes use of many of these circuit specializations. Bipolar cells, in response to glutamate release from cone photoreceptors, provide highly-sensitive glutamatergic input to amacrine cells and DS ganglion cells (DSGCs) in this circuit, while amacrine cells provide cholinergic and directionally-tuned GABAergic input to DSGCs. One population of DSGCs also transmit signals laterally to one another via gap junctions. Thus numerous specializations in bipolar cells, amacrine cells and ganglion cells endow DSGCs with their unique encoding abilities. In Chapters 2 and 3 of this dissertation I focus on synchronized firing between gap junction-coupled DSGCs. sDSGCs exhibit fine-scale correlations, with action potentials in an sDSGC more likely within ~2ms of action potential firing in a coupled neighbour. I first characterize electrical coupling of DSGCs through the identification of the molecular composition of DSGC gap junctions (Chapter 2). Physiological and immunohistochemical methods allowed me to demonstrate an important role for connexin 36 subunits in DSGC electrical coupling. Next (Chapter 3) I investigate the sub-cellular mechanisms underlying neuronal correlations between electrically coupled DSGCs. Using paired recordings, I show that chemical input (from bipolar cells and amacrine cells), electrical input (from gap junctions), and Na+ channel activity in DSGC dendrites underlie the generation of correlated spiking activity. While a common feature of electrically coupled networks, the mechanisms underlying correlations were previously unclear. In Chapter 4 I focus on the mechanisms within the DS circuit that endow these neurons with impressive sensitivity to stimulus contrast. Using physiological and pharmacological methods I first assess the relative contrast sensitivity of ganglion cells and starburst amacrine cells (SACs) in the DS circuit. The sensitivity of DSGC and SAC excitatory currents to antagonists of Na+ channels suggests an important role for these channels in amplifying low contrast responses and other weak inputs to the circuit. This role is later attributed to the differential expression of voltage-gated Na+ channels in specific bipolar cell populations. In aggregate, this dissertation describes several novel circuit mechanisms within the well-studied DS circuit. I also provide specific roles for such specializations in visual coding. / Graduate