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

Todd, William D; Venner, Anne; Anaclet, Christelle; Broadhurst, Rebecca Y; De Luca, Roberto; Bandaru, Sathyajit S; Issokson, Lindsay; Hablitz, Lauren M et al. · Nat Commun · 2020

basic_science · Level V

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

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