Non-rapid eye movement sleep determines resilience to social stress
- Morehouse School of Medicine, United States
- Walter Reed Army Institute of Research, United States
- University of California, Los Angeles, United States
Abstract
Resilience, the ability to overcome stressful conditions, is found in most mammals and varies significantly among individuals. A lack of resilience can lead to the development of neuropsychiatric and sleep disorders, often within the same individual. Despite extensive research into the brain mechanisms causing maladaptive behavioral-responses to stress, it is not clear why some individuals exhibit resilience. To examine if sleep has a determinative role in maladaptive behavioral-response to social stress, we investigated individual variations in resilience using a social-defeat model for male mice. Our results reveal a direct, causal relationship between sleep amount and resilience-demonstrating that sleep increases after social-defeat stress only occur in resilient mice. Further, we found that within the prefrontal cortex, a regulator of maladaptive responses to stress, pre-existing differences in sleep regulation predict resilience. Overall, these results demonstrate that increased NREM sleep, mediated cortically, is an active response to social-defeat stress that plays a determinative role in promoting resilience. They also show that differences in resilience are strongly correlated with inter-individual variability in sleep regulation.
Data availability
Data generated in this study are deposited in Dryad.
-
Non-rapid eye movement sleep determines resilience to social stressDryad Digital Repository, doi:10.5061/dryad.x0k6djhn4.
Article and author information
Author details
J Christopher Ehlen
Funding
National Institute of General Medical Sciences (GM127260)
- J Christopher Ehlen
National Institute on Minority Health and Health Disparities (Pilot funding,MD007602)
- J Christopher Ehlen
National Institute of Neurological Disorders and Stroke (NS078410)
- Ketema N Paul
National Heart, Lung, and Blood Institute (Graduate Student Fellowship,HL103104)
- Brittany J Bush
National Heart, Lung, and Blood Institute (Graduate Student Fellowship,HL007901)
- Eva-Jeneé A Andrews
National Heart, Lung, and Blood Institute (Postdoctoral Fellowship,HL117929)
- Cloe L Gray
National Heart, Lung, and Blood Institute (Postdoctoral Fellowship,HL116077)
- Allison J Brager
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Matthew N Hill, University of Calgary, Canada
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to a protocol (21-02) approved by the Morehouse School of Medicine institutional animal care and use committee (IACUC). All surgery was performed under isoflurane anesthesia, and analgesia was provided. Every effort was made to minimize pain and suffering.
Version history
- Received: May 12, 2022
- Preprint posted: June 1, 2022 (view preprint)
- Accepted: September 21, 2022
- Accepted Manuscript published: September 23, 2022 (version 1)
- Accepted Manuscript updated: September 26, 2022 (version 2)
- Version of Record published: October 21, 2022 (version 3)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Metrics
-
- 2,562
- views
-
- 490
- downloads
-
- 7
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Non-rapid eye movement sleep determines resilience to social stress
eLife 11:e80206.
https://doi.org/10.7554/eLife.80206
Further reading
-
- Neuroscience
Vesicles within presynaptic terminals are thought to be segregated into a variety of readily releasable and reserve pools. The nature of the pools and trafficking between them is not well understood, but pools that are slow to mobilize when synapses are active are often assumed to feed pools that are mobilized more quickly, in a series. However, electrophysiological studies of synaptic transmission have suggested instead a parallel organization where vesicles within slowly and quickly mobilized reserve pools would separately feed independent reluctant- and fast-releasing subdivisions of the readily releasable pool. Here, we use FM-dyes to confirm the existence of multiple reserve pools at hippocampal synapses and a parallel organization that prevents intermixing between the pools, even when stimulation is intense enough to drive exocytosis at the maximum rate. The experiments additionally demonstrate extensive heterogeneity among synapses in the relative sizes of the slowly and quickly mobilized reserve pools, which suggests equivalent heterogeneity in the numbers of reluctant and fast-releasing readily releasable vesicles that may be relevant for understanding information processing and storage.
-
- Evolutionary Biology
- Neuroscience
Neuropeptides are ancient signaling molecules in animals but only few peptide receptors are known outside bilaterians. Cnidarians possess a large number of G protein-coupled receptors (GPCRs) – the most common receptors of bilaterian neuropeptides – but most of these remain orphan with no known ligands. We searched for neuropeptides in the sea anemone Nematostella vectensis and created a library of 64 peptides derived from 33 precursors. In a large-scale pharmacological screen with these peptides and 161 N. vectensis GPCRs, we identified 31 receptors specifically activated by 1 to 3 of 14 peptides. Mapping GPCR and neuropeptide expression to single-cell sequencing data revealed how cnidarian tissues are extensively connected by multilayer peptidergic networks. Phylogenetic analysis identified no direct orthology to bilaterian peptidergic systems and supports the independent expansion of neuropeptide signaling in cnidarians from a few ancestral peptide-receptor pairs.
