title: Sleep alterations following exposure to stress predict fear-associated memory impairments in a rodent model of PTSD.
abstract: Sleep abnormalities, such as insomnia, nightmares, hyper-arousal, and difficulty initiating or maintaining sleep, are diagnostic criteria of posttraumatic stress disorder (PTSD). The vivid dream state, rapid eye movement (REM) sleep, has been implicated in processing emotional memories. We have hypothesized that REM sleep is maladaptive in those suffering from PTSD. However, the precise neurobiological mechanisms regulating sleep disturbances following trauma exposure are poorly understood. Using single prolonged stress (SPS), a well-validated rodent model of PTSD, we measured sleep alterations in response to stressor exposure and over a subsequent 7-day isolation period during which the PTSD-like phenotype develops. SPS resulted in acute increases in REM sleep and transition to REM sleep, and decreased waking in addition to alterations in sleep architecture. The severity of the PTSD-like phenotype was later assessed by measuring freezing levels on a fear-associated memory test. Interestingly, the change in REM sleep following SPS was significantly correlated with freezing behavior during extinction recall assessed more than a week later. Reductions in theta (4-10 Hz) and sigma (10-15 Hz) band power during transition to REM sleep also correlated with impaired fear-associated memory processing. These data reveal that changes in REM sleep, transition to REM sleep, waking, and theta and sigma power may serve as sleep biomarkers to identify individuals with increased susceptibility to PTSD following trauma exposure.
authors.affiliation: Department of Anesthesiology, University of Michigan, 7433 Medical Sciences Building 1, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Vanderheyden
authors.forename: Sophie A
authors.initials: SA
authors.lastname: George
authors.forename: Lea
authors.initials: L
authors.lastname: Urpa
authors.forename: Michaela
authors.initials: M
authors.lastname: Kehoe
authors.forename: Israel
authors.initials: I
authors.lastname: Liberzon
authors.forename: Gina R
authors.initials: GR
authors.lastname: Poe
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D015415:Biomarkers; D058256:Brain Waves / Q000502:physiology*; D004195:Disease Models, Animal; D005108:Extinction, Psychological; D005239:Fear / Q000502:physiology*; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology*; D011939:Mental Recall; D051381:Rats; D020318:Rats, Long-Evans; D012893:Sleep Wake Disorders / Q000209:etiology / Q000503:physiopathology*; D012895:Sleep, REM / Q000502:physiology*; D013313:Stress Disorders, Post-Traumatic / Q000150:complications / Q000503:physiopathology*
chemical_list: D015415:Biomarkers