A gut-secreted peptide suppresses arousability from sleep

Iris Titos; Alen Juginović; Alexandra Vaccaro; Keishi Nambara; Pavel Gorelik; Ofer Mazor; Dragana Rogulja

doi:10.1016/j.cell.2023.02.022

A gut-secreted peptide suppresses arousability from sleep

Iris Titos, Alen Juginović, Alexandra Vaccaro, Keishi Nambara, Pavel Gorelik, Ofer Mazor, Dragana Rogulja^*

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

Suppressing sensory arousal is critical for sleep, with deeper sleep requiring stronger sensory suppression. The mechanisms that enable sleeping animals to largely ignore their surroundings are not well understood. We show that the responsiveness of sleeping flies and mice to mechanical vibrations is better suppressed when the diet is protein rich. In flies, we describe a signaling pathway through which information about ingested proteins is conveyed from the gut to the brain to help suppress arousability. Higher protein concentration in the gut leads to increased activity of enteroendocrine cells that release the peptide CCHa1. CCHa1 signals to a small group of dopamine neurons in the brain to modulate their activity; the dopaminergic activity regulates the behavioral responsiveness of animals to vibrations. The CCHa1 pathway and dietary proteins do not influence responsiveness to all sensory inputs, showing that during sleep, different information streams can be gated through independent mechanisms.

Original language	English (US)
Pages (from-to)	1382-1397.e21
Journal	Cell
Volume	186
Issue number	7
DOIs	https://doi.org/10.1016/j.cell.2023.02.022
State	Published - Mar 30 2023

Funding

We thank our lab and Michael Crickmore’s lab for advice and comments on the manuscript. Benjamin Sanchez developed the software used to control mechanical stimuli and analyze behavioral responsiveness. Alexa Soares assisted with the screen. Alejandra Laureano assisted with the mouse experiments. For fly stocks, we thank Michael Crickmore, Nicholas Stavropoulos, Kyunghee Koh, and Norbert Perrimon. We thank Pedro Saavedra for assistance with the quantitative RT-PCR. Schematics were created with the help of BioRender.com . I.T. was supported by the Mahoney and Brooks postdoctoral fellowships. D.R. is a New York Stem Cell – Robertson investigator. This work was supported by the New York Stem Cell Foundation , the NIH ( DP2 OD022385 ), and the Pew Scholars Program in the Biomedical Sciences .

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2023.02.022

Cite this

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abstract = "Suppressing sensory arousal is critical for sleep, with deeper sleep requiring stronger sensory suppression. The mechanisms that enable sleeping animals to largely ignore their surroundings are not well understood. We show that the responsiveness of sleeping flies and mice to mechanical vibrations is better suppressed when the diet is protein rich. In flies, we describe a signaling pathway through which information about ingested proteins is conveyed from the gut to the brain to help suppress arousability. Higher protein concentration in the gut leads to increased activity of enteroendocrine cells that release the peptide CCHa1. CCHa1 signals to a small group of dopamine neurons in the brain to modulate their activity; the dopaminergic activity regulates the behavioral responsiveness of animals to vibrations. The CCHa1 pathway and dietary proteins do not influence responsiveness to all sensory inputs, showing that during sleep, different information streams can be gated through independent mechanisms.",

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AU - Gorelik, Pavel

AU - Mazor, Ofer

AU - Rogulja, Dragana

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A gut-secreted peptide suppresses arousability from sleep

Abstract

Funding

ASJC Scopus subject areas

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