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Endogenous oxytocin inhibits hypothalamic corticotrophin‐releasing hormone neurones following acute hypernatraemia

Dipanwita Pati,Scott W. Harden,Wanhui Sheng,Kyle B Kelly,Annette D. de Kloet,E. Krause,C. Frazier

Published 2020 in Journal of neuroendocrinology

ABSTRACT

Significant prior evidence indicates that centrally acting oxytocin robustly modulates stress responsiveness and anxiety‐like behaviour, although the neural mechanisms behind these effects are not entirely understood. A plausible neural basis for oxytocin‐mediated stress reduction is via inhibition of corticotrophin‐releasing hormone (CRH) neurones in the paraventricular nucleus of the hypothalamus (PVN) that regulate activation of the hypothalamic‐pituitary‐adrenal axis. Previously, we have shown that, following s.c. injection of 2.0 mol L−1 NaCl, oxytocin synthesising neurones are activated in the rat PVN, an oxytocin receptor (Oxtr)‐dependent inhibitory tone develops on a subset of parvocellular neurones and stress‐mediated increases in plasma corticosterone levels are blunted. In the present study, we utilised transgenic male CRH‐reporter mice to selectively target PVN CRH neurones for whole‐cell recordings. These experiments reveal that acute salt loading produces tonic inhibition of PVN CRH neurones through a mechanism that is largely independent of synaptic activity. Further studies reveal that a subset of CRH neurones within the PVN synthesise mRNA for Oxtr(s). Salt induced Oxtr‐dependent inhibitory tone was eliminated in individual PVN CRH neurones filled with GDP‐β‐S. Additional electrophysiological studies suggest that reduced excitability of PVN CRH neurones in salt‐loaded animals is associated with increased activation of inwardly rectifying potassium channels. Nevertheless, substantial effort to recapitulate the core effects of salt loading by activating Oxtr(s) with an exogenous agonist produced mixed results. Collectively, these results enhance our understanding of how oxytocin receptor‐mediated signalling modulates the function of CRH neurones in the PVN.

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