Regulation of Hypothalamic CRH Neuron Excitability by Oxytocin

Abstract

Oxytocin (OT) is a neuropeptide that exerts multiple actions throughout the brain and periphery. Within the brain, OT regulates diverse neural populations, including neural networks controlling responses to stress. Local release of OT within the paraventricular nucleus (PVN) of the hypothalamus has been suggested to regulate stress responses by modulating the excitability of neighboring corticotropin-releasing hormone (CRH) neurons. However, the mechanisms by which OT regulates CRH neuron excitability are unclear. Here, we investigated the morphological relationship between OT and CRH neurons and determined the effects of OT on CRH neuron excitability. Morphological analysis revealed that the processes of OT and CRH neurons were highly intermingled within the PVN, possibly allowing for local cell-to-cell cross talk. Whole-cell patch-clamp recordings from CRH neurons was used to study the impact of OT on postsynaptic excitability and synaptic innervation. Bath-applied OT did not alter CRH neuron holding current, spiking output or any action potential parameters. Recordings of evoked excitatory and inhibitory postsynaptic currents (EPSCs/IPSCs) revealed no net effect of OT on current amplitude, however, subgroups of CRH neurons appeared to respond differentially to OT. Analysis of spontaneous EPSC events uncovered a significant reduction in spontaneous EPSC frequency but no change in spontaneous EPSC amplitude in response to OT. Together these data demonstrate that OT exerts a subtle modulation of synaptic transmission onto CRH neurons providing one potential mechanism by which OT could suppress CRH neuron excitability and stress axis activity.

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