TY - JOUR
T1 - Timekeeping in the hindbrain
T2 - a multi-oscillatory circadian centre in the mouse dorsal vagal complex
AU - Chrobok, Lukasz
AU - Northeast, Rebecca C.
AU - Myung, Jihwan
AU - Cunningham, Peter S.
AU - Petit, Cheryl
AU - Piggins, Hugh D.
N1 - Funding Information:
This work was supported by a project grant BB/M02329X from the BBSRC (UK) to HDP and a MRC DTP Studentship to RCN. LC was additionally supported by a Polish National Science Centre doctoral scholarship “Etiuda IV” 2016/20/T/NZ4/00273. JM was supported by the Taiwan Ministry of Science and Technology (107-2311-B-038-001-MY2, 107-2410-H-038-004-MY2, 108-2321-B006-023-MY2, 108-2410-H-038-008-MY2), the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan, Taipei Medical University (TMU107-AE1-B15, 107-3805-003-110), Taipei Medical University-Shuang Ho Hospital (107TMU-SHH-03), and Nakayama Foundation for Human Science. We would like to thank Tomasz Blasiak, PhD (Jagiellonian University in Krakow, Poland) for sharing his custom-made MatLab scripts and expertise in the analysis of electrophysiological data. Drs. Ashleigh Wilcox, David Lyons, and Giuseppe D’Agostino provided valuable comments on earlier drafts of the manuscript. We thank the staff of the University of Manchester Biological Services Facility and Bioimaging Facility for their assistance.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Metabolic and cardiovascular processes controlled by the hindbrain exhibit 24 h rhythms, but the extent to which the hindbrain possesses endogenous circadian timekeeping is unresolved. Here we provide compelling evidence that genetic, neuronal, and vascular activities of the brainstem’s dorsal vagal complex are subject to intrinsic circadian control with a crucial role for the connection between its components in regulating their rhythmic properties. Robust 24 h variation in clock gene expression in vivo and neuronal firing ex vivo were observed in the area postrema (AP) and nucleus of the solitary tract (NTS), together with enhanced nocturnal responsiveness to metabolic cues. Unexpectedly, we also find functional and molecular evidence for increased penetration of blood borne molecules into the NTS at night. Our findings reveal that the hindbrain houses a local network complex of neuronal and non-neuronal autonomous circadian oscillators, with clear implications for understanding local temporal control of physiology in the brainstem.
AB - Metabolic and cardiovascular processes controlled by the hindbrain exhibit 24 h rhythms, but the extent to which the hindbrain possesses endogenous circadian timekeeping is unresolved. Here we provide compelling evidence that genetic, neuronal, and vascular activities of the brainstem’s dorsal vagal complex are subject to intrinsic circadian control with a crucial role for the connection between its components in regulating their rhythmic properties. Robust 24 h variation in clock gene expression in vivo and neuronal firing ex vivo were observed in the area postrema (AP) and nucleus of the solitary tract (NTS), together with enhanced nocturnal responsiveness to metabolic cues. Unexpectedly, we also find functional and molecular evidence for increased penetration of blood borne molecules into the NTS at night. Our findings reveal that the hindbrain houses a local network complex of neuronal and non-neuronal autonomous circadian oscillators, with clear implications for understanding local temporal control of physiology in the brainstem.
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U2 - 10.1038/s42003-020-0960-y
DO - 10.1038/s42003-020-0960-y
M3 - Article
AN - SCOPUS:85084289521
SN - 2399-3642
VL - 3
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 225
ER -