Non-rapid eye movement sleep determines resilience to social stress

  1. Brittany J Bush
  2. Caroline Donnay
  3. Eva-Jeneé A Andrews
  4. Darielle Lewis-Sanders
  5. Cloe L Gray
  6. Zhimei Qiao
  7. Allison J Brager
  8. Hadiya Johnson
  9. Hamadi CS Brewer
  10. Sahil Sood
  11. Talib Saafir
  12. Morris Benveniste
  13. Ketema N Paul
  14. J Christopher Ehlen  Is a corresponding author
  1. Neuroscience Institute, Morehouse School of Medicine, United States
  2. Behavioral Biology Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, United States
  3. Department of Integrative Biology and Physiology, University of California, Los Angeles, United States
6 figures, 1 table and 1 additional file

Figures

Figure 1 with 1 supplement
Daily sleep-restriction prevents resilience to social-defeat stress.

One cohort of mice received sleep restriction (8 hr, beginning at light onset) on each day of social-defeat stress; a second cohort (sleep replete) received only social-defeat stress (A; 10 days …

Figure 1—figure supplement 1
Aggressive encounters during 10 – days of social-defeat stress.

The number of aggressive approaches was counted during each 5-min exposure to social-defeat stress and totaled for the entire 10-day period. Box and whiskers plots represent the median number of …

Figure 2 with 1 supplement
Increased sleep promotes resilience to social-defeat stress.

Adeno-associated viral vectors (AAV2) encoding either an excitatory (Gq) designer receptor exclusively activated by designer drugs (DREADD), or enhanced green fluorescent protein (EGFP) as a …

Figure 2—figure supplement 1
Histological verification of designer-receptor exclusively activated by designer-drugs (DREADD).

Verification of pAAV-hSyn-EGFP (control, not shown) or pAAV-hSyn-hM3D(Gq)-mCherry (excitatory DREADD) expression was performed in sections with nucleic-acid counter stain (DAPI). Representative …

Figure 3 with 1 supplement
Sleep is reorganized only in mice resilient to social-defeat stress.

24 hr sleep recordings were performed both before and following 10 days of social-defeat stress (A). Sleep in animals identified as resilient (B) was significantly reorganized (C) and increased (D) …

Figure 3—figure supplement 1
Sleep is not reorganized after exposure to a novel cage.

24 hr sleep recordings were performed both before and following 10-daily exposures to a novel cage (A). This was done to control for the novel environment experienced during social-defeat stress. …

Figure 4 with 1 supplement
Differences in sleep regulation, prior to social-defeat stress exposure, predicts resilience to social-defeat stress.

Sleep regulation involves a homeostatic process, as NREM sleep amount and intensity (slow-wave activity, SWA) are proportional to the duration of prior wakefulness. A standard method for …

Figure 4—figure supplement 1
Sleep fragmentation before and after social-defeat stress.

Sleep fragmentation was assessed from 24 hr recordings during undisturbed sleep and with a six-hour sleep restriction. Recordings were performed both before and after 10 days of social-defeat stress …

Figure 5 with 1 supplement
Sleep changes in the ventromedial prefrontal cortex (vmPFC) predict resilience to social-defeat stress.

Local field potential (LFP) in the vmPFC and epidural electroencephalographic recordings (EEG; A, top row; black bars on x-axis=p ≤ 0.05) were simultaneously obtained from mice before ten-days of …

Figure 5—figure supplement 1
Power density in resilient vs susceptible animals and sleep changes in the ventromedial prefrontal cortex.

Simultaneous local-field potential (LFP)recordings in the ventromedial prefrontal cortex and electroencephalographic (EEG) recordings were obtained from mice before (A) and after (B) 10-days of …

NREM coherence in the 0.5–4 Hz range predicts resilience to social-defeat stress.

Local field potential (LFP) in the ventromedial prefrontal cortex and epidural electroencephalographic recordings (EEG) were simultaneously obtained from mice before and after 10-days of …

Tables

Key resources table
Reagent type (species) or resourceDesignationSource or referenceIdentifiersAdditional information
Strain, strain background (Mus musculus, male)C57BL/6 JJackson Labs, Bar Harbor, ME.Stock #: 000664
Strain, strain background (Mus musculus, male)CD-1; retired breedersCharles Rivers Laboratories, Willington, MA.0022CD1Used as aggressors in social defeat
Recombinant DNA reagentControl Vehicle, DREADD-, pAAV-hSyn-EGFPAddgene, Watertown, MA.Plasmid #50465
Recombinant DNA reagentExcitatory DREADD, DREADD +, pAAV-hSyn-hM3D(Gq)-mCherryAddgene, Watertown, MA.Plasmid #50474
Commercial assay or kitCorticosterone ELISA KitCayman Chemical, Ann Arbor, MI.Item No. 501320
Chemical compound, drugClozapine N Oxide; CNOHello Bio Princeton, NJ.Cat# HB6149Dosage: 2 mg/kg
Software, algorithmSirenia AcquisitionPinnacle Technology Inc, Lawrence, KS.Version 1.8.3
Software, algorithmSirenia SleepPinnacle Technology Inc Lawrence, KS.Version 1.8.3
Software, algorithmSleep Deprivation SystemPinnacle Technology Inc, Lawrence, KS.Cat. #: 9000-K5-S
Software, algorithmIgor Pro 8 software 64-bitWaveMetrics, Inc, Lake Oswego, OR.Version 8.04FilterIIR, DSPPeriodogram and custom scripts.
Software, algorithm,Noldus Ethovision XTNoldus Information Technology, Leesburg, VA.Version 14Video tracking during social avoidance test.
Software, algorithmGraphPad PrismGraphPad Software, San Deigo CA.Version 7.00
OtherPrefabricated Electroencephalographic Implant; EEG; electromyograph; EMGPinnacle Technologies Inc, Lawrence, KS.Cat. #: 8201-SS; 8431Materials for surgery (Surgery: EEG and LFP electrodes section).
OtherStainless steel screw electrodesPinnacle Technology Inc Lawrence, KS.Cat. #: 8209, 8212, 8403Materials for surgery(Surgery: EEG and LFP electrodes section).
OtherSilver EpoxyPinnacle Technology Inc Lawrence, KS.Cat. #:8226Materials for surgery(Surgery: EEG and LFP electrodes section).

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