Stress-induced sleep-like inactivity modulates stress susceptibility in mice

Abstract

Severe environmental and social stress induces dysregulation of sleep along with mood and cognitive disturbances. However, the role and mechanism of this sleep dysregulation remain elusive. Here we evaluated sleep-like inactivity measured by voluntary movements and its relationship to social behaviors in mice without or with social defeat stress as well as the stressed mice with subsequent sleep deprivation. Social defeat stress immediately induced sleep-like inactivity with decreased body temperature. In the social interaction test, the control mice showed high social interest and its correlation with social sniffing intensity, the latter of which indicates positive valence of social sniffing. After the stress, these social characteristics were maintained in stress-resilient mice, but disrupted in stress-susceptible mice, leading to social avoidance. Sleep deprivation after the stress decreased social sniffing intensity along with reduced social interest, but enhanced the exploratory activity with the positive valence of social sniffing. We also found by c-Fos immunohistochemistry that the stress activated sleep-related brain regions, the dorsomedial hypothalamus and ventrolateral periaqueductal gray. Collectively, these findings show that stress activates sleep-related brain regions and induces sleep-like inactivity, contributing to multiple roles of stress-induced sleep for social behaviors.

Chronic social defeat stress increases the amounts of 12-lipoxygenase lipid metabolites in the nucleus accumbens of stress-resilient mice

“…The social interaction test was performed as previously described 4 , 9 , 12 , 30 . One day before the first stress exposure, an experimental mouse was habituated for 150 s to an open rectangle chamber (30 cm × 40 cm) with an empty metal meshwork placed at one end.…”

Long-Term Effects of Repeated Social Defeat Stress on Brain Activity during Social Interaction in BALB/c Mice

“…To examine the long-term effects of repeated SDS on brain activity in BALB/c mice, we focused on c-Fos, a marker of neuronal excitation (Hudson, 2018; for review, see Herrera and Robertson, 1996). The expression of c-Fos immediately after the SDS session is well investigated (Tanaka et al, 2012;Nasanbuyan et al, 2018;Numa et al, 2019;Nagai et al, 2020). In such analyses, however, it is difficult to distinguish the psychological effects of stress and the direct effects of physical injury caused by SDS.…”

On the Mental Status of Stargazer Mice

“…"Sleep" epochs were defined as contiguous periods of immobility lasting ≥40s, previously validated to provide >90% agreement with neurophysiologically-determined sleep. [30][31][32][33] WT (n = 24, 9 female) and mutants (n = 26, 16 female) were studied in cohorts of 8-15 mice. A modular design 19 was applied beginning with a 2hlong initial habituation study ("Intro") and two consecutive 23h long baseline recordings each beginning at 1400.…”

“…"Sleep" epochs were defined as contiguous periods of immobility lasting ≥40s, previously validated to provide >90% agreement with neurophysiologically-determined sleep. [30][31][32][33] WT (n = 24, 9 female)…”

“…To more granularly examine changes in arousal, we applied an established and validated noninvasive method which estimates "sleep" as periods of sustained immobility lasting ≥ 40s. 19,20,[30][31][32][33] Under these criteria, mutants displayed shorter and more frequent bouts of "sleep", without an overall change in total "sleep". These differences primarily affected the ~35% of all "sleep" bouts longer than ~230s, while the timing of "sleep" bouts throughout the day was unchanged (Figure 2D).…”