# Defining the role of sleep in resilience to social stress

> **NIH NIH SC1** · MOREHOUSE SCHOOL OF MEDICINE · 2021 · $355,000

## Abstract

Sleep disorders are a pervasive feature of a wide variety of neuropsychiatric conditions, and social stress is
known to cause or exacerbate both sleep and neuropsychiatric disorders; however, it is not known how sleep is
involved in regulating the limbic structures and circuits that control resilience to social stress. The long-term goal
of this work is to determine the role of sleep in regulating maladaptive behavior. The overall objective of this
application is to understand the mechanistic role of sleep in the limbic circuits that regulate resilience to social
stress. These studies use a mouse model wherein sustained social avoidance occurs following social-defeat
stress. Preliminary data from this model are the first to demonstrate that development of social avoidance can
be predicted by differences in sleep regulation that exist before exposure to social stress. Furthermore, these
data demonstrate that increased sleep occurring after social-defeat stress is associated with resilience to social
avoidance. The central hypothesis of these studies is that increased sleep following social-defeat stress is a
resilience response that protects against defeat-induced changes in the mPFC known to result in maladaptive
behavior. In order to test this hypothesis the application pursues the following specific aims: 1) Determine if
cortical differences in sleep amount, mPFC electrophysiology and sleep homeostasis underlie resilience to social
defeat stress; 2) Determine if sleep plays a causal role in the development of defeat-induced social-avoidance;
and 3) Determine if sex-differences in the homeostatic regulation of sleep underlie sex-differences in resilience.
In the first aim, a detailed analysis will be performed on electroencephalographic recordings from the cortex and
local field potential recordings from the mPFC recorded in mice identified as either resilient or susceptible to the
effects of social-defeat stress. This will include an analysis of these signals in both the frequency and time domain
along with the measurement of homeostatic responses to sleep deprivation. In the second aim, sleep will be
prevented or promoted (using sleep deprivation or chemogenetics, respectively) at multiple time-points pre, post
and during defeat. This will determine if sleep is sufficient and/or necessary for preventing the behavioral con-
sequences of social-defeat stress. This aim will also characterize the effect of sleep manipulations on molecular
changes in the limbic system, namely ΔFosB, associated with resilience and susceptibility. The third aim will
focus on developing a female model with which to study the role of sleep in resilience and will begin to conduct
investigations with this model. The approach proposed in this application is innovative because it aims to char-
acterize sleep in both resilient and susceptible populations of mice. The contributions of the proposed research
will be significant because it is expected to yield a mechanistic mod...

## Key facts

- **NIH application ID:** 10169462
- **Project number:** 5SC1GM127260-04
- **Recipient organization:** MOREHOUSE SCHOOL OF MEDICINE
- **Principal Investigator:** John Christopher Ehlen
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $355,000
- **Award type:** 5
- **Project period:** 2018-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169462

## Citation

> US National Institutes of Health, RePORTER application 10169462, Defining the role of sleep in resilience to social stress (5SC1GM127260-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10169462. Licensed CC0.

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