Abstract
There is a strong circadian rhythm of corticosteroid secretion in animals and humans, but the circuit for translating the suprachiasmatic (SCN) clock light-dark cycle rhythm into an increase in corticosteroid secretion beginning several hours before the active period is not known. We show here that in male mice, this rhythm depends upon input from the SCN to the subparaventricular zone (SPZ), and then to the dorsomedial nucleus of the hypothalamus (DMH). Both glutamatergic and GABAergic DMH neurons are required for the daily surge of corticosteroid secretion in anticipation of the active period. Glutamatergic DMH neurons directly excite paraventricular nucleus corticotrophin-releasing hormone (PVH-CRH) neurons, whereas DMH GABA neurons disinhibit PVH-CRH neurons via a relay in GABAergic neurons in the caudoventral PVH. This circuit underlies the daily surge in corticosteroid secretion that is temporally linked but phase advanced compared to the SCN activity cycle.
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The data generated in this study are provided in the Source Data file. Source data are provided with this paper.
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Acknowledgements
This study was supported by NIH grants: R01 NS122589-03 and P01HL149630-04 to E.A. P01HL149630-04 and R01 NS085477 to C.B.S., and R03 NS128993-02 to RDL. The authors thank Quan Ha and Sathyajit Bandaru for the superb technical assistance.
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O.D.R-P., R.D.L., E.A., and C.B.S. designed research; O.D.R-P., R.D.L., N. L. S. M., D.E., M.A.K., S.S.B., N.V., and F.R. performed research; O.D.R-P., R.D.L., and E.A. analyzed data; C.B.S. contributed to the project administration and funding acquisition; O.D.R-P., R.D.L., E.A., and C.B.S. wrote the paper, and all the authors approved the final version. O.D.R-P., R.D.L., equally contributed to this study. E.A. and C.B.S. share senior authorship.
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Ramirez-Plascencia, O.D., De Luca, R., Machado, N.L.S. et al. A hypothalamic circuit for circadian regulation of corticosterone secretion. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71482-0
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DOI: https://doi.org/10.1038/s41467-026-71482-0
