SEROTONIN REGULATES GAP JUNCTION COUPLING IN THE DEVELOPING RAT SOMATOSENSORY CORTEX

To further elucidate the role of the neuromodulatory transmitter serot onin (5-HT) during early postnatal development of the neocortex, we in vestigated the effects of 5-HT on gap junction coupling in the somatos ensory cortex of rats aged between postnatal days 7 and 10. The gap ju nction-permeable tracer neurobiotin was injected into single neurons v ia microelectrodes or patch pipettes. Under control conditions, cluste rs of about 25 tracer-coupled neurons were observed. Serotonin reduced dye-coupling between lamina II/III pyramidal cells in a concentration -dependent and reversible manner. The 1,4,5-inositol triphosphate (IP3 ) receptor antagonist heparin as well as the protein kinase C inhibito r NPC 15437 suppressed the uncoupling action of 5-HT, suggesting that the serotonergic effect involved IP3 receptor-mediated release of calc ium ions from intracellular stores. In contrast, the 5-HT-induced redu ction in gap junction coupling was not antagonized by Rp-adenosine-3', 5'-cyclic monophosphothionate, an inhibitor of cAMP dependent protein kinase. The uncoupling effect of 5-HT was mimicked by 5-HT2 receptor a gonists and antagonized by the 5-HT2 receptor antagonist ritanserin, i ndicating that 5-HT suppressed gap junction coupling via activation of 5-HT2 class receptors. Our results suggest that the developmental fun ctions of 5-HT not only involve the modulation of chemical synaptic tr ansmission but also include the regulation of the gap junctional commu nication system during differentiation of the neocortex.