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

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 (SCN VIP )-producing neurons to PVN corticotropin-releasing hormone (PVN CRH )-producing neurons. PVN CRH 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 PVN CRH calcium activity and dramatically reduces the amplitude and precision of daily corticosterone release. SCN VIP activation reduces (and inactivation increases) corticosterone release and PVN CRH calcium activity, and daily SCN VIP activation entrains PVN clock gene rhythms by inhibiting PVN CRH neurons. We conclude that daily corticosterone release depends on coordinated clock gene and neuronal activity rhythms in both SCN VIP and PVN CRH neurons.