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Published July 30, 2020 | Version v1
Dataset Open

Data from: Hypothalamic circuitry underlying stress-induced insomnia and peripheral immunosuppression

Description

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. As stress is further associated with changes in immune function, we used single-cell mass cytometry by time of flight (CyTOF) to analyze peripheral blood and found extensive changes to immune cell distribution and functional responses during wakefulness upon optogenetic stimulation of CRHPVN neurons. Our findings suggest both central and peripheral systems are synergistically engaged in the response to stress via CRHPVN circuitry.

Notes

The files are in .fcs (flow cytometry standard) format. The files contain discrete events (each one is a cell or bead) detected by the cytof machine. Each event can be associated with any number of antibodies in the panel, a palladium barcode, and DNA intercalator staining.

Control group files are labelled with CRH_Cre. Stimulated group files are labelled with CRH_Cre_10Hz.

Funding provided by: National Institutes of Health
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: R01 MH102638

Funding provided by: Stanford Alzheimer's Disease Center - Scully Family Seed Grant*
Crossref Funder Registry ID:
Award Number: P50AG047366

Funding provided by: Stanford Department of Psychiatry and Behavioral Sciences Innovator Seed Grant*
Crossref Funder Registry ID:
Award Number:

Funding provided by: National Institute of Mental Health
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000025
Award Number: F32 MH115431

Funding provided by: Stanford Department of Anesthesiology (FIDL grant)*
Crossref Funder Registry ID:
Award Number:

Funding provided by: National Institutes of Health
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: R01 MH116470

Funding provided by: National Institutes of Health
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: R01 HL150566

Funding provided by: Stanford Alzheimer's Disease Center - Scully Family Seed Grant
Crossref Funder Registry ID:
Award Number: P50AG047366

Funding provided by: Stanford Department of Psychiatry and Behavioral Sciences Innovator Seed Grant
Crossref Funder Registry ID:

Funding provided by: Stanford Department of Anesthesiology (FIDL grant)
Crossref Funder Registry ID:

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