Abstract
Significant prior evidence indicates that centrally acting oxytocin robustly modulates stress responsiveness and anxiety-like behavior, although the neural mechanisms behind these effects are not completely understood. A plausible neural basis for oxytocin mediated stress reduction is via inhibition of corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) that regulate activation of the hypothalamic-pituitary-adrenal (HPA) axis. Previously, we have shown that following subcutaneous injection of 2.0 M NaCl, oxytocin (OT) synthesizing neurons are activated in the rat PVN, an oxytocin receptor (Oxtr) dependent inhibitory tone develops on a subset of parvocellular neurons, and stress-mediated increases in plasma corticosterone levels are blunted. Here, we utilized transgenic male CRH-reporter mice to selectively target PVN CRH neurons for whole-cell recordings. These experiments reveal that acute salt loading produces tonic inhibition of PVN CRH neurons through a mechanism that is largely independent of synaptic activity. Further studies reveal that CRH neurons within the PVN synthesize mRNA for Oxtr(s). Salt induced Oxtr-dependent inhibitory tone was eliminated in individual PVN CRH neurons filled with GDP-β-S, and was also largely absent in PVN CRH neurons extracted form CRH-Oxtr KO mice. Additional electrophysiological studies suggest that reduced excitability of PVN CRH neurons in salt loaded animals is associated with increased activation of an inwardly rectifying potassium channel. Collectively, these data reveal a likely cellular mechanism by which endogenous oxytocin signaling reduces the excitability of PVN CRH neurons to curb stress responsiveness during times of high plasma osmolality.
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