POSTSYNAPTIC MECHANISM OF DEPRESSION OF GABAERGIC SYNAPSES BY OXYTOCIN IN THE SUPRAOPTIC NUCLEUS OF IMMATURE RAT

1. Oxytocin is known to act on autoreceptors of oxytocin neurones in t he supraoptic nucleus (SON). We investigated whether oxytocin modulate s putative oxytocin neurones by suppressing the GABA(A) receptor-media ted synaptic inputs on these cells. 2. GABAergic inhibitory postsynapt ic currents (IPSCs) were recorded from SON neurones in hypothalamic sl ices from young rats. Oxytocin specifically reduced the amplitude of b oth spontaneous and evoked IPSCs, without altering their current kinet ics. 3. The effect of oxytocin was observed in 70% of the magnocellula r neurones recorded from the dorsomedial part of the SON. d(CH2)(5)OVT , a specific antagonist of oxytocin receptors, blocked the effect of o xytocin on the IPSCs. Vasopressin had no effect on oxytocin-sensitive SON neurones. 4. The intervals between spontaneous IPSCs were not affe cted by oxytocin. This suggested that oxytocin had a postsynaptic effe ct on SON neurones. 5. This postsynaptic origin was further substantia ted by application of TTX, which blocked all evoked release but did no t prevent the suppressive effect of oxytocin on the amplitude of the s pontaneous IPSCs still present in the recording. The selective effect of oxytocin on IPSC amplitude was also maintained in nominally zero ex tracellular calcium. 6. Intracellular perfusion of SON neurones with G TP gamma S mimicked the effect of oxytocin on IPSCs, while GDP beta S, similarly applied, abolished the effect of oxytocin. 7. Application o f calcium mobilizers such as thapsigargin and caffeine also reduced th e amplitude of spontaneous IPSCs without significantly altering the fr equency at which IPSCs occurred. 8. Thus, oxytocin depresses GABAergic synapses in the SON via modulation of the postsynaptic GABA(A) recept ors. This would lead to disinhibition of SON neurones sensitive to oxy tocin and could, therefore, be a powerful means of controlling the fir ing of oxytocin neurones.