Nitric Oxide Modulation of Supraoptic Oxytocin and Vasopressin Neurons Involves Potentiation of Gabaergic Synaptic Inputs.
There is growing evidence that nitric oxide (NO) in the central nervous system functions as a local neuromodulator in water balance and osmotic regulation. However, the precise mechanisms by which these actions are mediated are still poorly understood. Neuronal nitric oxide synthase (nNOS) is abundantly expressed in the supraoptic (SON) and paraventricular (PVN) nuclei. nNOS expression is up-regulated in conditions known to stimulate oxytocin (OT) and vasopressin (VP) hormone release, such as salt loading and water deprivation. Since several studies have shown that NO mainly decreases the excitability of OT and VP neurons, NO may function as a local inhibitory feedback on activated SON neurons. In the present study we combined in vivo and in vitro electrophysiological studies to investigate whether NO-induced inhibition of SON neurons is mediated by activation of GABAergic inputs in the SON. In vivo retrodialysis of the NO-donor SNP into the SON inhibited the firing activity of both OT and VP neurons. This inhibition was largely blocked by retrodialysis of the GABAA receptor antagonist bicuculline. In order to understand the cellular mechanisms linking NO and GABAergic systems in the SON, in vitro patch clamp recordings of GABAA synaptic currents were obtained from immunochemically identified neurons in hypothalamic slices. The frequency and amplitude of miniature GABAA synaptic currents in both OT and VP neurons were significantly increased by SNP. These results suggest that NO inhibition of neuronal excitability of OT and VP neurons is largely mediated by pre- and postsynaptic potentiation of GABAergic synaptic activity in the SON. Thus, the proposed NO-GABAergic inhibitory feedback in the SON might constitute an important mechanism by which NO regulates osmotic and fluid balance homeostasis.