Suprachiasmatic VIP neurons are required for normal circadian rhythmicity and comprised of molecularly distinct subpopulations.

Abstract:

: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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Todd WD,Venner A,Anaclet C,Broadhurst RY,De Luca R,Bandaru SS,Issokson L,Hablitz LM,Cravetchi O,Arrigoni E,Campbell JN,Allen CN,Olson DP,Fuller PM

doi

10.1038/s41467-020-17197-2

subject

Has Abstract

pub_date

2020-09-02 00:00:00

pages

4410

issue

1

issn

2041-1723

pii

10.1038/s41467-020-17197-2

journal_volume

11

pub_type

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