Trauma exposure and sleep: using a rodent model to understand sleep function in PTSD

Abstract

Post-traumatic stress disorder (PTSD) is characterized by intrusive memories of a traumatic event, avoidance behavior related to cues of the trauma, emotional numbing, and hyper-arousal. Sleep abnormalities and nightmares are core symptoms of this disorder. In this review, we propose a model which implicates abnormal activity in the locus coeruleus (LC), an important modifier of sleep-wake regulation, as the source of sleep abnormalities and memory abnormalities seen in PTSD. Abnormal LC activity may be playing a key role in symptom formation in PTSD via sleep dysregulation and suppression of hippocampal bidirectional plasticity.

The Spectral Fingerprint of Sleep Problems in Post-Traumatic Stress Disorder

“…Of note, REM sleep has also been related to memory reprocessing, in particular regarding emotional memories (14,(73)(74)(75). A comprehensive account of how observed physiological changes during REM and NREM sleep in PTSD might lead to erratic memory consolidation with 'runaway' characteristics, is given in a recent review (76).…”

Context Processing and the Neurobiology of Post-Traumatic Stress Disorder

“…Hippocampal-prefrontal communication involves additional nodes in the midline thalamus, such as the reuniens and rhomboid nuclei, which participate in consolidation of enduring memories at a systems level (Pereira de Vasconcelos and Cassel, 2015). This process requires sleep-specific field-potential oscillations occurring during slow-wave rapid eye movement sleep (REM), which, in turn, rely upon specific function of locus coeruleus (LC) neurons (Vanderheyden et al, 2014). Thus effective encoding, consolidation, updating, and retrieval of contextual memory within hippocampal-prefrontal-thalamic circuitry likely require appropriate modulation by LC firing.…”

“…During REM and TR, to allow bi-directional plasticity (Poe et al, 2010), the noradrenergic (NE) neurons in the LC must turn off, which is essential for synaptic depotentiation (Thomas et al, 1996; Booth and Poe, 2006). If a hyperadrenergic state is present during REM and TR, the necessary synaptic depotentiation would be impaired, disrupting the rewiring of memory networks in the hippocampus (Vanderheyden et al, 2014), and potentially contributing to emergence of contextual processing abnormalities. The origins of the “hyperadrenergic state” could be partly genetic, given the ADRB2 findings in PTSD (Liberzon et al, 2014), which may thus contribute to development of deficits in hippocampal-prefrontal-thalamic circuit function.…”

Sleep alterations following exposure to stress predict fear-associated memory impairments in a rodent model of PTSD

“…However, the precise electrophysiological properties of sleep that accompany trauma exposure remain poorly understood. Disturbances in REM sleep have been hypothesized to be a hallmark feature of PTSD (Ross et al 1989; Germain 2013; Vanderheyden et al 2014) due to the critical role of REM sleep in emotional regulation and memory consolidation (Walker 2009; Walker and van der Helm 2009; Wellman et al 2013), both of which are impaired in PTSD. However, many trauma-exposed individuals never develop PTSD, and it is unknown whether sleep plays a role in mediating resilience or susceptibility to this disorder.…”

“…Specifically, theta band (4–10Hz) activity during REM sleep is higher in humans who are resilient to PTSD acquisition following trauma exposure compared with those that develop PTSD. Theta band (Merica and Blois 1997; Mitchell et al 2008), and sigma band (10–15 Hz) activity (Tamminen et al 2010; Watts et al 2012) plays a critical role in sleep-dependent memory consolidation processes, making these EEG frequencies important candidate biomarkers of PTSD severity, though their link with PTSD development has only been posited thus far (Vanderheyden et al 2014). …”