TY - JOUR
T1 - Suprachiasmatic VIP neurons are required for normal circadian rhythmicity and comprised of molecularly distinct subpopulations
AU - Todd, William D.
AU - Venner, Anne
AU - Anaclet, Christelle
AU - Broadhurst, Rebecca Y.
AU - De Luca, Roberto
AU - Bandaru, Sathyajit S.
AU - Issokson, Lindsay
AU - Hablitz, Lauren M.
AU - Cravetchi, Olga
AU - Arrigoni, Elda
AU - Campbell, John N.
AU - Allen, Charles N.
AU - Olson, David P.
AU - Fuller, Patrick M.
N1 - Funding Information:
We gratefully acknowledge the expert assistance of Lauren Sohn, Tilar Martin, Megan Gray, Cameron Friedman, Minh Ha, and Quan Ha. We also gratefully acknowledge Naomi Habib for training in sNuc-Seq, and Rachael Ivison of the Boston Nutrition Obesity Research Center (BNORC) Functional Genomics and Bioinformatics Core for sNuc-Seq data processing. Funding was provided by Alzheimer’s Association grant AARF-16-443613 and R03AG062883-01 to W.D.T., Sleep Research Society grant CDA 016-JP-17 to A.V., K99MH103399 to C.A., an American Diabetes Association Pathway to Stop Diabetes award 1-18-INI-14 and pilot and feasibility studies from the Boston Nutrition Obesity Research Center (under a grant from the National Institutes of Health, NIH; award number P30 DK046200) and from the Boston Area Diabetes Endocrinology Research Center (BADERC; NIH, under award number P30DK057521) to J.N.C., NIDA Training Grant Postdoctoral Fellowship T32DA007262 to L.M.H., NS091126 to E.A., NS036607 and NS103842 to C.N.A., DK071561 and DK104999 to D.P.O., and NS073613, NS092652 and NS103161 to P.M.F.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - The hypothalamic suprachiasmatic (SCN) clock contains several neurochemically defined cell groups that contribute to the genesis of circadian rhythms. Using cell-specific and genetically targeted approaches we have confirmed an indispensable role for vasoactive intestinal polypeptide-expressing SCN (SCNVIP) neurons, including their molecular clock, in generating the mammalian locomotor activity (LMA) circadian rhythm. Optogenetic-assisted circuit mapping revealed functional, di-synaptic connectivity between SCNVIP neurons and dorsomedial hypothalamic neurons, providing a circuit substrate by which SCNVIP neurons may regulate LMA rhythms. In vivo photometry revealed that while SCNVIP neurons are acutely responsive to light, their activity is otherwise behavioral state invariant. Single-nuclei RNA-sequencing revealed that SCNVIP neurons comprise two transcriptionally distinct subtypes, including putative pacemaker and non-pacemaker populations. Altogether, our work establishes necessity of SCNVIP neurons for the LMA circadian rhythm, elucidates organization of circadian outflow from and modulatory input to SCNVIP cells, and demonstrates a subpopulation-level molecular heterogeneity that suggests distinct functions for specific SCNVIP subtypes.
AB - The hypothalamic suprachiasmatic (SCN) clock contains several neurochemically defined cell groups that contribute to the genesis of circadian rhythms. Using cell-specific and genetically targeted approaches we have confirmed an indispensable role for vasoactive intestinal polypeptide-expressing SCN (SCNVIP) neurons, including their molecular clock, in generating the mammalian locomotor activity (LMA) circadian rhythm. Optogenetic-assisted circuit mapping revealed functional, di-synaptic connectivity between SCNVIP neurons and dorsomedial hypothalamic neurons, providing a circuit substrate by which SCNVIP neurons may regulate LMA rhythms. In vivo photometry revealed that while SCNVIP neurons are acutely responsive to light, their activity is otherwise behavioral state invariant. Single-nuclei RNA-sequencing revealed that SCNVIP neurons comprise two transcriptionally distinct subtypes, including putative pacemaker and non-pacemaker populations. Altogether, our work establishes necessity of SCNVIP neurons for the LMA circadian rhythm, elucidates organization of circadian outflow from and modulatory input to SCNVIP cells, and demonstrates a subpopulation-level molecular heterogeneity that suggests distinct functions for specific SCNVIP subtypes.
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U2 - 10.1038/s41467-020-17197-2
DO - 10.1038/s41467-020-17197-2
M3 - Article
C2 - 32879310
AN - SCOPUS:85090092192
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 4410
ER -