Responses of magnocellular neurons to osmotic stimulation involves coactivation of excitatory and inhibitory input: An experimental and theoretical analysis

How does a neuron, challenged by an increase in synaptic input, display a r esponse that is independent of the initial level of activity? Here we show that both oxytocin and vasopressin cells in the supraoptic nucleus of norma l rats respond to intravenous infusions of hypertonic saline with gradual, linear increases in discharge rate. In hyponatremic rats, oxytocin and vaso pressin cells also responded linearly to intravenous infusions of hypertoni c saline but with much lower slopes. The linearity of response was surprisi ng, given both the expected nonlinearity of neuronal behavior and the nonli nearity of the oxytocin secretory response to such infusions. We show that a simple computational model can reproduce these responses well, but only i f it is assumed that hypertonic infusions coactivate excitatory and inhibit ory synaptic inputs. This hypothesis was tested first by applying the GABA( A) antagonist bicuculline to the dendritic zone of the supraoptic nucleus b y microdialysis. During local blockade of GABA inputs, the response of oxyt ocin cells to hypertonic infusion was greatly enhanced. We then went on to directly measure GABA release in the supraoptic nucleus during hypertonic i nfusion, confirming the predicted rise. Together, the results suggest that hypertonic infusions lead to coactivation of excitatory and inhibitory inpu ts and that this coactivation may confer appropriate characteristics on the output behavior of oxytocin cells. The nonlinearity of oxytocin secretion that accompanies the linear increase in oxytocin cell firing rate reflects frequency-facilitation of stimulus-secretion coupling at the neurohypophysi s.