Oxytocin receptors excite lateral nucleus of central amygdala by phospholipase Cβ- and protein kinase C-dependent depression of inwardly rectifying K+ channels.

Abstract

Activation of oxytocin receptors (OXTRs) facilitates neuronal excitability in rat lateral nucleus of central amygdala (CeL). OXTR-induced excitation is mediated by inhibition of inwardly rectifying K+ (Kir) channels. Phospholipase Cβ is necessary for OXTR-mediated excitation of CeL neurons and depression of Kir channels. OXTR-elicited depression of Kir channels and excitation of CeL neurons require the function of Ca2+ -dependent protein kinase C. Oxytocin (OXT) is a nonapeptide that exerts anxiolytic effects in the brain. The amygdala is an important structure involved in the modulation of fear and anxiety. A high density of OXT receptors (OXTRs) has been detected in the capsular (CeC) and lateral (CeL) nucleus of the central amygdala (CeA). Previous studies have demonstrated that activation of OXTRs induces remarkable increases in neuronal excitability in the CeL/C. However, the signalling and ionic mechanisms underlying OXTR-induced facilitation of neuronal excitability have not been determined. We found that activation of OXTRs in the CeL increased action potential firing frequency recorded from neurons in this region via inhibition of the inwardly rectifying K+ channels. The functions of phospholipase Cβ and protein kinase C were required for OXTR-induced augmentation of neuronal excitability. Our results provide a cellular and molecular mechanism whereby activation of OXTRs exerts anxiolytic effects.