Fear conditioning fragments REM sleep in stress-sensitive Wistar–Kyoto, but not Wistar, rats

Abstract

Pavlovian conditioning is commonly used to investigate the mechanisms of fear learning. Because the Wistar-Kyoto (WKY) rat strain is particularly stress-sensitive, we investigated the effects of a psychological stressor on sleep in WKY compared to Wistar (WIS) rats. Male WKY and WIS rats were either fear-conditioned to tone cues or received electric foot shocks alone. In the fearconditioning procedure, animals were exposed to 10 tones (800 Hz, 90 dB, 5 sec), each coterminating with a foot shock (1.0 mA, 0.5 sec), at 30-sec intervals. In the shock stress procedure, animals received 10 foot shocks at 30-sec intervals, without tones. All subjects underwent a toneonly test both 24 hrs (Day 1) and again two weeks (Day 14) later. Rapid eye movement sleep (REMS) continuity was investigated by partitioning REMS episodes into single (inter-REMS episode interval > 3 min) and sequential (interval ≤ 3 min) episodes. In the fear-conditioned group, freezing increased from baseline in both strains, but the increase was maintained on Day 14 in WKY rats only. In fear-conditioned WKY rats, total REMS amount increased on Day 1, sequential REMS amount increased on Day 1 and Day 14, and single REMS amount decreased on Day 14. Alterations were due to changes in the number of sequential and single REMS episodes. Shock stress had no significant effect on REMS microarchitecture in either strain. The shift toward sequential REMS in fear-conditioned WKY rats may represent REMS fragmentation, and may provide a model for investigating the neurobiological mechanisms of sleep disturbances reported in posttraumatic stress disorder.

Early-life trauma is associated with rapid eye movement sleep fragmentation among military veterans

“…Previous work has identified more proximal associations between trauma exposure, and REM sleep disturbance among humans (Habukawa et al, 2007; Mellman et al, 2002), also replicated in the current study; however, the current work demonstrates the prolonged influence that earlier-life trauma may have on the development of REM sleep physiology. This finding replicates, and thus translates to humans, similar findings previously described by experimental animal models that identified the prolonged effect that fear-conditioning has on sleep physiology (DaSilva et al, 2011; Madan et al, 2008). Furthermore, earlier-life trauma was independently associated with REM sleep fragmentation whereas later-life trauma was limited to a non-significant trend.…”

The basolateral amygdala can mediate the effects of fear memory on sleep independently of fear behavior and the peripheral stress response

“…Mellman et al have suggested that PTSD may be linked to reductions in REM following trauma and to subsequent increases over time as additional processes promote REM in ways that may assist recovery (Mellman, Kobayashi, Lavela, Wilson, and Hall Brown, 2014). Others have suggested that the lack of a strong phasic REM sleep response after a stressful event could predispose to the later increase in REM sleep phasic activity that has been observed in humans with chronic PTSD (DaSilva, Lei, Madan, Mann, Ross, Tejani-Butt, and Morrison, 2011). All of these suggestions, as well as findings from our work in animals, are consistent with REM playing a significant role in mediating stress-related emotion.…”

Impaired extinction of fear conditioning after REM deprivation is magnified by rearing in an enriched environment

“…Brennan, Pawlyk, Ross, & Morrison, 2005;Kumar & Jha, 2012;Sanford et al, 2003) or produces REM fragmentation (DaSilva et al, 2011;Madan et al, 2008). However, REM returns to normal following successful extinction of fear responses (Wellman et al, 2008).…”