Vasopressin facilitates GABAergic transmission in rat hippocampus via activation of V1A receptors

Whereas vasopressin has been shown to enhance memory possibly by increasing long-term potentiation and direct excitation of the pyramidal neurons in the hippocampus, the effects of vasopressin on GABAergic transmission in the hippocampus remain to be determined. Here we examined the effects of vasopressin on GABAergic transmission onto CA1 pyramidal neurons and our results demonstrate that bath application of [Arg8]-vasopressin (AVP) dose-dependently increased the frequency of spontaneous IPSCs (sIPSCs) recorded from CA1 pyramidal neurons via activation of V1A receptors. Immunohistological staining and western blot further confirmed that both CA1 pyramidal neurons and interneurons expressed V1A receptors. Bath application of AVP altered neither the frequency nor the amplitude of miniature IPSCs in the presence of tetradotoxin and failed to change significantly the amplitude of evoked IPSCs recorded from CA1 pyramidal neurons. AVP increased the firing frequency of action potentials by depolarizing the GABAergic interneurons in the stratum radiatum of CA1 region. AVP-mediated depolarization of interneurons was mediated by inhibition of a background K+ conductance which was insensitive to extracellular tetraethylammonium, Cs+, 4-aminopyridine, tertiapin-Q and Ba2+. AVP-induced depolarization of interneurons was dependent on Gαq/11 but independent of phospholipase C, intracellular Ca2+ release and protein kinase C. The inhibitory effects of AVP-mediated modulation of GABA release onto CA1 pyramidal neurons were overwhelmed by its strong excitation of CA1 pyramidal neurons in physiological condition but revealed when its direct excitation of the pyramidal neurons was blocked suggesting that AVP-mediated modulation of GABAergic transmission fine-tunes the excitability of CA1 pyramidal neurons.

► We examine the effects of vasopressin on GABAergic transmission in the hippocampus.
► Vasopressin increases GABA release via activation of V1A receptors.
► Vasopressin depolarizes GABAergic interneurons via inhibition of K+ channels.
► Vasopressin-induced depolarization is dependent on Gαq/11.
► Functions of PLC and PKC are not required.