Abstract

Sleep disturbances are commonly found in trauma-exposed populations. Additionally, trauma exposure results in fear-associated memory impairments. Given the interactions of sleep with learning and memory, we hypothesized that increasing sleep duration following trauma exposure would restore overall function and improve trauma-induced fear-associated memory dysfunction. Here, we utilized single prolonged stress, a validated rodent model of post-traumatic stress disorder, in combination with optogenetic activation of hypothalamic melanin-concentrating hormone containing cells to increase sleep duration. The goal of this work was to ascertain if post-trauma sleep increases are sufficient to improve fear-associated memory function. In our laboratory, optogenetic stimulation after trauma exposure was sufficient to increase REM sleep duration during both the Light and Dark Phase, whereas NREM sleep duration was only increased during the Dark Phase of the circadian day. Interestingly though, animals that received optogenetic stimulation showed significantly improved fear-associated memory processing compared to non-stimulated controls. These results suggest that sleep therapeutics immediately following trauma exposure may be beneficial and that post-trauma sleep needs to be further examined in the context of the development of post-traumatic stress disorder.

Highlights

  • Sleep disturbances are commonly found in trauma-exposed populations

  • We found no difference in baseline sleep in either the control rAAV expressing or non-stimulated Channelrhodopsin-2 gene (ChR2) expressing animals from non-virus injected animals, indicating that injection of virus alone had no effect on baseline sleep duration

  • Optogenetic stimulation of the rAAV-MCHChR2-EGFP expressing animals resulted in increased rapid eye movement (REM) sleep during both the Dark and Light phase and increased Dark phase non-rapid eye movement (NREM) sleep increases that replicate the results from previously published work with these two ­viruses[25]

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Summary

Introduction

Sleep disturbances are commonly found in trauma-exposed populations. trauma exposure results in fear-associated memory impairments. We utilized single prolonged stress, a validated rodent model of post-traumatic stress disorder, in combination with optogenetic activation of hypothalamic melanin-concentrating hormone containing cells to increase sleep duration. Though, animals that received optogenetic stimulation showed significantly improved fear-associated memory processing compared to non-stimulated controls These results suggest that sleep therapeutics immediately following trauma exposure may be beneficial and that post-trauma sleep needs to be further examined in the context of the development of post-traumatic stress disorder. Humans resilient to PTSD show increased theta activity during rapid eye movement (REM) s­ leep[10] and reduced autonomic nervous system activation as measured by changes in heart rate during quiescent ­periods[12,13] These data suggest a reciprocal relationship between sleep and PTSD wherein trauma exposure impairs sleep and sleep disorders increase the severity of ­PTSD14. Fear-associated memory tests are a functional metric for confirmation of PTSD in this pre-clinical PTSD model

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