# Sleep and PTSD

> **NIH VA I01** · HARRY S. TRUMAN MEMORIAL VA HOSPITAL · 2020 · —

## Abstract

Posttraumatic stress disorder (PTSD) is a multifaceted disorder precipitated by exposure to a
psychologically distressing event. Although, diagnostic symptoms for PTSD include hyperarousal, re-
experiencing (flashbacks/nightmares), and avoidance, sleep disruptions are considered the hallmark of
PTSD. PTSD affects a large proportion of military personnel and veterans and is associated with numerous
deleterious outcomes for veterans and active duty service personnel. The costs of PTSD to the individual
and society are substantial.
Strong evidence, from clinical and preclinical studies, suggest a dysregulation of brain regions and
behavioral systems related to fear memory processes in the etiology and symptomatology of PTSD. Thus,
to understand the pathophysiology of PTSD and to develop efficacious treatment strategies, it is important
to understand the neurobiology of fear memory system.
It is well established that sleep is critical for fear and extinction memory consolidation. Our recent studies
suggests that the sleep-promoting melanin-concentrating hormone (MCH) mediates the effects of sleep on
fear memory consolidation. Mice exposed to predator odor trauma show protracted sleep disruption along
with contextual fear conditioning. However, pharmacogenetic silencing of MCH neurons or blockade of
MCH receptors in the hippocampus or amygdala, immediately after fear memory acquisition, normalizes
sleep and attenuates fear.
In this proposal, we propose to extend our research and examine molecular mechanisms mediating the
effects of MCH on fear memory. Since changes in the epigenome are the basis of memory consolidation,
we hypothesized that MCH acts via MCH receptor and mitogen activated protein kinase (MAPK) signaling
cascade to perturb the epigenome and consolidate, reconsolidate and promote extinction of fear memories.
We will use wild type and transgenic (expressing Cre-recombinase under MCH promoter control) C57BL/6J
mice as our animal model and contextual fear conditioning, with predator odor as unconditional stimulus, to
examine consolidation, reconsolidation and extinction of fear memories.
Our first aim proposes that pharmacogenetic silencing of MCH neurons or blockade of MCH receptors will
attenuate MAPK signaling, reduce histone acetylation and BDNF expression, which will result in the
attenuation of memory consolidation and normalization of sleep. Pharmacogenetic silencing of MCH
neurons coupled with infusion of MCH peptide, in the hippocampus or amygdala, will block the effects of
MCH neuronal silencing and promote fear.
Our second aim proposes that MCH reconsolidates contextual fear memories by enhancing the expression
of Zif268, in the hippocampus and amygdala, via MAPK signaling cascade. Pharmacogenetic silencing of
MCH neurons or blockade of MCH receptor in the hippocampus or amygdala, immediately after fear
reactivation, will attenuate MAPK signaling and Zif268 expression, which will attenuate fear reconsolidation.
In contrast, infus...

## Key facts

- **NIH application ID:** 9781956
- **Project number:** 2I01BX002661-05
- **Recipient organization:** HARRY S. TRUMAN MEMORIAL VA HOSPITAL
- **Principal Investigator:** Pradeep Kumar Sahota
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2015-10-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9781956

## Citation

> US National Institutes of Health, RePORTER application 9781956, Sleep and PTSD (2I01BX002661-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9781956. Licensed CC0.

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