Cholecystokinin neurons in mouse suprachiasmatic nucleus regulate the robustness of circadian clock

Lucheng Xie; Yangyang Xiong; Danyi Ma; Kaiwen Shi; Jiu Chen; Qiaoqiao Yang; Jun Yan

doi:10.1016/j.neuron.2023.04.016

Cholecystokinin neurons in mouse suprachiasmatic nucleus regulate the robustness of circadian clock

Neuron. 2023 Jul 19;111(14):2201-2217.e4. doi: 10.1016/j.neuron.2023.04.016. Epub 2023 May 11.

Authors

Lucheng Xie¹, Yangyang Xiong¹, Danyi Ma², Kaiwen Shi², Jiu Chen², Qiaoqiao Yang³, Jun Yan⁴

Affiliations

¹ Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Shanghai 200031, China.
² Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.
³ Department of Neurosurgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
⁴ Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 201210, China; School of Future Technology, University of Chinese Academy of Sciences, Beijing 101408, China. Electronic address: junyan@ion.ac.cn.

PMID: 37172583
DOI: 10.1016/j.neuron.2023.04.016

Abstract

The suprachiasmatic nucleus (SCN) can generate robust circadian behaviors in mammals under different environments, but the underlying neural mechanisms remained unclear. Here, we showed that the activities of cholecystokinin (CCK) neurons in the mouse SCN preceded the onset of behavioral activities under different photoperiods. CCK-neuron-deficient mice displayed shortened free-running periods, failed to compress their activities under a long photoperiod, and developed rapid splitting or became arrhythmic under constant light. Furthermore, unlike vasoactive intestinal polypeptide (VIP) neurons, CCK neurons are not directly light sensitive, but their activation can elicit phase advance and counter light-induced phase delay mediated by VIP neurons. Under long photoperiods, the impact of CCK neurons on SCN dominates over that of VIP neurons. Finally, we found that the slow-responding CCK neurons control the rate of recovery during jet lag. Together, our results demonstrated that SCN CCK neurons are crucial for the robustness and plasticity of the mammalian circadian clock.

Keywords: SCN; cholecystokinin; circadian clock; clock neurons; jet lag; photoperiod; seasonality.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cholecystokinin*
Circadian Clocks*
Circadian Rhythm / physiology
Mammals / metabolism
Mice
Neurons / physiology
Photoperiod
Suprachiasmatic Nucleus / metabolism
Vasoactive Intestinal Peptide / metabolism

Substances

Cholecystokinin
Vasoactive Intestinal Peptide