Kisspeptin activation of supraoptic nucleus neurons in vivo

Oxytocin and vasopressin are synthesized by magnocellular neurosecretory cells in the hypothalamic supraoptic and paraventricular nuclei and are released from the posterior pituitary gland into the circulation. Intravenous administration of the ligand for the G protein-coupled receptor 54 receptor, kisspeptin-10, increases plasma oxytocin levels and intracerebroventricular kisspeptin-10 increases vasopressin levels, indicating that kisspeptin might play a role in various physiological functions via stimulation of oxytocin and vasopressin secretion. Because posterior pituitary hormone secretion is dependent on action potential (spike) discharge, we used in vivo extracellular single unit recording to determine the effects of kisspeptin-10 on supraoptic nucleus neurons in urethane-anaesthetized female rats. Intravenous kisspeptin-10 (100 μg) increased the firing rate of oxytocin neurons from 3.7 ± 0.8 to 4.7 ± 0.8 spikes/sec (P = 0.0004), but only a quarter of vasopressin neurons responded to iv kisspeptin-10, showing a short (<3 sec) high-frequency (>15 spikes/sec) burst of firing. By contrast, intracerebroventricular kisspeptin-10 (2 and 40 μg) did not alter oxytocin or vasopressin neuron firing rate. To investigate the pathway involved in the peripheral action of kisspeptin-10, we used i.p. capsaicin to desensitize vagal afferents, which prevented the i.v. kisspeptin-10-induced increase of oxytocin neuron firing rate. This is the first report to show that peripheral, but not central, kisspeptin-10 increases the activity of oxytocin neurons and a proportion of vasopressin neurons and that endogenous kisspeptin regulation of supraoptic nucleus neurons is likely via vagal afferent input, with kisspeptin acting as a hormone rather than as a neuropeptide in this system.