Involvement of TRPC5 channels, inwardly rectifying K+ channels, PLCβ and PIP2 in vasopressin-mediated excitation of medial central amygdala neurons

Key points Activation of V-1a vasopressin receptors facilitates neuronal excitability in the medial nucleus of central amygdala (CeM) V-1a receptor activation excites about 80% CeM neurons by opening a cationic conductance and about 20% CeM neurons by suppressing an inwardly rectifying K+ (Kir) channel The cationic conductance activated by V-1a receptors is identified as TRPC5 channels PLC beta-mediated depletion of PIP2 is involved in V-1a receptor-elicited excitation of CeM neurons Intracellular Ca2+ release and PKC are unnecessary for V-1a receptor-mediated excitation of CeM neurons Arginine vasopressin (AVP) serves as a hormone in the periphery to modulate water homeostasis and a neuromodulator in the brain to regulate a diverse range of functions including anxiety, social behaviour, cognitive activities and nociception. The amygdala is an essential brain region involved in modulating defensive and appetitive behaviours, pain and alcohol use disorders. Whereas activation of V-1a receptors in the medial nucleus of the central amygdala (CeM) increases neuronal excitability, the involved ionic and signalling mechanisms have not been determined. We found that activation of V-1a receptors in the CeM facilitated neuronal excitability predominantly by opening TRPC5 channels, although AVP excited about one fifth of the CeM neurons via suppressing an inwardly rectifying K+ (Kir) channel. G proteins and phospholipase C beta (PLC beta) were required for AVP-elicited excitation of CeM neurons, whereas intracellular Ca2+ release and the activity of protein kinase C were unnecessary. Prevention of the depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) blocked AVP-induced excitation of CeM neurons, suggesting that PLC beta-mediated depletion of PIP2 is involved in AVP-mediated excitation of CeM neurons. Our results may provide a cellular and molecular mechanism to explain the anxiogenic effects of AVP in the amygdala.