University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Department of Neurobiology; Anaclet Lab

Publication Date

2020-09-02

Document Type

Article

Disciplines

Neuroscience and Neurobiology

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 (SCN(VIP)) neurons, including their molecular clock, in generating the mammalian locomotor activity (LMA) circadian rhythm. Optogenetic-assisted circuit mapping revealed functional, di-synaptic connectivity between SCN(VIP) neurons and dorsomedial hypothalamic neurons, providing a circuit substrate by which SCN(VIP) neurons may regulate LMA rhythms. In vivo photometry revealed that while SCN(VIP) neurons are acutely responsive to light, their activity is otherwise behavioral state invariant. Single-nuclei RNA-sequencing revealed that SCN(VIP) neurons comprise two transcriptionally distinct subtypes, including putative pacemaker and non-pacemaker populations. Altogether, our work establishes necessity of SCN(VIP) neurons for the LMA circadian rhythm, elucidates organization of circadian outflow from and modulatory input to SCN(VIP) cells, and demonstrates a subpopulation-level molecular heterogeneity that suggests distinct functions for specific SCN(VIP) subtypes.

Keywords

Circadian mechanisms, Circadian regulation

Rights and Permissions

© The Author(s) 2020. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.

DOI of Published Version

10.1038/s41467-020-17197-2

Source

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. Suprachiasmatic VIP neurons are required for normal circadian rhythmicity and comprised of molecularly distinct subpopulations. Nat Commun. 2020 Sep 2;11(1):4410. doi: 10.1038/s41467-020-17197-2. PMID: 32879310; PMCID: PMC7468160. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Nature communications

PubMed ID

32879310

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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