CONNEXIN-36-CONTAINING GAP JUNCTIONS TUNE OSCILLATION DYNAMICS AND MEDIATE NETWORK STABILITY IN RAT HYPOTHALAMIC DOPAMINE NEURONS

Electrical coupling through gap junctions (GJs) strategically connects discrete populations of neurons throughout the central nervous system. While these intercellular channels connect the cytoplasm of one cell to another, allowing the bidirectional passage of current and small molecules, the impact of GJs on network dynamics is understudied. Here, we investigated this issue in hypothalamic neuroendocrine Tuberoinfundibular Dopamine (TIDA) neurons, which control pituitary release of the hormone prolactin (Prl). Rat TIDA neurons exhibit stereotyped slow oscillations that are synchronised across the population through strong GJs (Stagkourakis, Pérez et. al., 2018). Nearly all rat TIDA neurons were found to express Connexin-36 (Cx36), the primary pore-forming protein of neuronal GJs. Next, a cre-dependent CRISPR-Cas9 system was used to knock out (K.O.) the Cx36 gene (GJD2) in male Tyrosine-Hydroxylase-Cre-expressing rats. In paired ex vivo patch clamp recordings, we observed loss of TIDA electrical coupling and synchrony upon K.O. Notably, TIDA oscillation dynamics were also disrupted, with lower rhythmicity, smaller oscillation amplitude, and a wider range of oscillation frequencies, suggesting that electrical coupling is critical in the establishment and maintenance of network dynamics rather than synchrony alone. TIDA oscillation properties dictate dopamine release and, subsequently, circulating Prl levels, with an impact on parental behaviours (Stagkourakis et. al., 2020). Thus, we are currently exploring the effects of Cx36 K.O. on serum Prl levels and on paternal behaviour in rats. This study provides experimental evidence that electrical synapses control the spatiotemporal features of network rhythms beyond mere synchrony.