Hypothalamic circuitry underlying stress-induced insomnia and peripheral immunosuppression.

Li, Shi-Bin, Borniger, Jeremy C, Yamaguchi, Hiroshi, Hédou, Julien, Gaudilliere, Brice, de Lecea, Luis (September 2020) Hypothalamic circuitry underlying stress-induced insomnia and peripheral immunosuppression. Science Advances, 6 (37). eabc2590-eabc2590. ISSN 2375-2548

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Abstract

The neural substrates of insomnia/hyperarousal induced by stress remain unknown. Here, we show that restraint stress leads to hyperarousal associated with strong activation of corticotropin-releasing hormone neurons in the paraventricular nucleus of hypothalamus (CRHPVN) and hypocretin neurons in the lateral hypothalamus (HcrtLH). CRHPVN neurons directly innervate HcrtLH neurons, and optogenetic stimulation of LH-projecting CRHPVN neurons elicits hyperarousal. CRISPR-Cas9-mediated knockdown of the crh gene in CRHPVN neurons abolishes hyperarousal induced by stimulating LH-projecting CRHPVN neurons. Genetic ablation of Hcrt neurons or crh gene knockdown significantly counteracts restraint stress-induced hyperarousal. Single-cell mass cytometry by time of flight (CyTOF) revealed extensive changes to immune cell distribution and functional responses in peripheral blood during hyperarousal upon optogenetic stimulation of CRHPVN neurons simulating stress-induced insomnia. Our findings suggest both central and peripheral systems are synergistically engaged in the response to stress via CRHPVN circuitry.

Item Type:	Paper
Subjects:	organism description > animal behavior organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions > tissues types and functions > suprachiasmatic nucleus > hypothalamus organs, tissues, organelles, cell types and functions > tissues types and functions > hypothalamus organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell organs, tissues, organelles, cell types and functions organism description > animal behavior > stress
CSHL Authors:	Borniger, Jeremy
Communities:	CSHL labs > Borniger lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	September 2020
Date Deposited:	30 Apr 2021 14:28
Last Modified:	21 Nov 2024 19:03
PMCID:	PMC11206529
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/39962

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