Pre- and postsynaptic modulation of the electrical activity of rat supraoptic neurones

The release of vasopressin and oxytocin is regulated by the electrical acti vity of magnocellular neurosecretory cells in the supraoptic and paraventri cular nuclei, which is under the control of a great variety of neurotransmi tters and neuromodulators. The major neural signals to the supraoptic nucle us are from excitatory glutamate inputs and inhibitory GABA inputs. In rece nt studies, the voltage-clamp mode of the whole-cell patch-clamp technique has been applied to slice preparations from rat hypothalamus to monitor syn aptic inputs to supraoptic neurones. Spontaneous excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) are abolished by CNQX and picrotoxi n, respectively, but are insensitive to tetrodotoxin, indicating that they represent quantal release of glutamate and GABA, respectively, from nerve t erminals of presynaptic neurones. GABA and glutamate show remarkable suppre ssive effects on both EPSCs and IPSCs via presynaptic GABA(B) and mGlu rece ptors, respectively. Noradrenaline, which excites supraoptic neurones via p ostsynaptic alpha(1)-receptors, also suppresses IPSCs and potentiates EPSCs . On the other hand, prostaglandin E-2, which excites supraoptic neurones v ia postsynaptic prostaglandin E-2 (EP) receptors of the EP4 subclass, also suppresses IPSCs via EP3 receptors but has little effect on EPSCs. Thus pre - and postsynaptic mechanisms may act cooperatively to excite supraoptic ne urones. Nitric oxide, which inhibits supraoptic neurones, potentiates IPSCs without affecting EPSCs. This provides another example for the preferentia l modulation of IPSCs of supraoptic neurones. On the other hand, PACAP, whi ch causes a long-lasting increase in the firing frequency via the postsynap tic receptors, has no effect on EPSCs and IPSCs, suggesting that some ligan ds act only at postsynaptic receptors. Thus multiple patterns for pre- and postsynaptic modulation are present in the supraoptic nucleus, and the elec trical activity of supraoptic neurones is regulated via complex mechanisms at both pre- and postsynaptic sites.