Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-020-17197-2
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Funding
- Alzheimer's Association [AARF-16-443613, R03AG062883-01]
- Sleep Research Society [CDA 016-JP-17, K99MH103399]
- American Diabetes Association [1-18-INI-14]
- Boston Nutrition Obesity Research Center (National Institutes of Health, NIH) [P30 DK046200]
- Boston Area Diabetes Endocrinology Research Center (BADERC
- NIH) [P30DK057521]
- NIDA Training Grant Postdoctoral Fellowship [T32DA007262, NS091126, NS036607, NS103842, DK071561, DK104999, NS073613, NS092652, NS103161]
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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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