Circadian neurons in the paraventricular nucleus entrain and sustain daily rhythms in glucocorticoids

Jeff R Jones,Erik D Herzog,Daniel Granados-Fuentes,Sneha Chaturvedi

doi:10.1038/s41467-021-25959-9

Abstract

Signals from the central circadian pacemaker, the suprachiasmatic nucleus (SCN), must be decoded to generate daily rhythms in hormone release. Here, we hypothesized that the SCN entrains rhythms in the paraventricular nucleus (PVN) to time the daily release of corticosterone. In vivo recording revealed a critical circuit from SCN vasoactive intestinal peptide (SCNVIP)-producing neurons to PVN corticotropin-releasing hormone (PVNCRH)-producing neurons. PVNCRH neurons peak in clock gene expression around midday and in calcium activity about three hours later. Loss of the clock gene Bmal1 in CRH neurons results in arrhythmic PVNCRH calcium activity and dramatically reduces the amplitude and precision of daily corticosterone release. SCNVIP activation reduces (and inactivation increases) corticosterone release and PVNCRH calcium activity, and daily SCNVIP activation entrains PVN clock gene rhythms by inhibiting PVNCRH neurons. We conclude that daily corticosterone release depends on coordinated clock gene and neuronal activity rhythms in both SCNVIP and PVNCRH neurons.

Highlights

Entrains rhythms in the paraventricular nucleus (PVN) to time the daily release of corticosterone
Discrete activation or inactivation of suprachiasmatic nucleus (SCN) vasoactive intestinal peptide (SCNVIP) neuron activity reliably alters the peak amplitude of corticosterone release and PVN corticotropin-releasing hormone (PVNCRH) neuron calcium activity, and daily SCNVIP activation entrains PVN clock gene rhythms by inhibiting PVNCRH neurons. These results demonstrate that the daily corticosterone surge depends on coordinated clock gene expression and neuronal activity rhythms in both SCNVIP and PVNCRH neurons
To determine whether the physiology of PVNCRH neurons changes with time of day, we developed methods to monitor clock gene expression and calcium activity in PVNCRH neurons in freely-behaving mice longitudinally and at high temporal resolution

Summary

Introduction

Entrains rhythms in the paraventricular nucleus (PVN) to time the daily release of corticosterone. The HPA axis regulates the body’s response to stress through corticotropinreleasing hormone (CRH)-producing neurons in the paraventricular nucleus of the hypothalamus (PVN), which promote the release of adrenocorticotropin hormone (ACTH) from the pituitary to induce the adrenal glands to produce glucocorticoids. This stress-induced activation of the HPA axis is superimposed on a baseline circadian release of glucocorticoids that is regulated by signals from the SCN to PVNCRH neurons that act to induce or suppress the release of ACTH25. Deleting SCNVIP neurons blunts corticosterone rhythms[42]

Methods

Results

Conclusion