Hsiao Sui-Wen, Doi Masao
Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Int Rev Cell Mol Biol. 2025;393:1-14. doi: 10.1016/bs.ircmb.2024.06.002. Epub 2024 Jun 26.
The suprachiasmatic nucleus (SCN) functions as the master circadian pacemaker in mammals. Since 2015, facilitated by cutting-edge optogenetic and chemogenetic techniques, significant progress has been made in understanding the circuits involving the SCN that mediate diverse physiological functions. The time-specific and cell type-selective manipulation of neuronal activity within and outside the SCN drove the verification of both expected and previously unrecognized circuits operating for controlling various functions, including circadian locomotor activity, itch behavior, anticipatory thirst, aggression, corticosterone release, food-anticipatory activity, wakefulness, and photoperiod-related adaptive behavior. In addition, optogenetic/chemogenetic approaches verified the functional connection of the SCN to the control of body temperature, heart rate, and insulin sensitivity through as-yet-unknown circuit details. This review intends to provide an overview of SCN input/output pathways elucidated by optogenetics and chemogenetics. A fundamental question remains regarding the coherence of the identified numerous output pathways that are dictated by the SCN. Deciphering the potential coordination among the SCN's circuits via optogenetics and chemogenetics is needed to understand the mechanism underlying the harmonious regulation of multiple circadian physiologies.