Chronic Mild Circadian Disruption Alters Anxiety-Like Behavior and Spatial Navigation in Adult Mice

Sleep and circadian disruption adversely impacts mental health and physiology. Such disruption varies in degree and emerges from numerous causes, ranging from severe disruption arising from rotating shift work or frequent jetlag to more mild circadian stress experienced by people with circadian rhythm sleep disorders (CRSD). While the effects of extreme circadian disruption such as jetlag are established through animal studies, less is understood about more subtle mismatches between external zeitgeber cycles and internal circadian periods as is observed with CRSDs. The present study employed a slightly mismatched ~1-h disruption paradigm, whereby Black and Tan BRachyury (BTBR) and C57BL/6 mice were housed from conception onwards in a conventional 24-h light/dark (LD) cycle or a 22.75-h LD cycle closer to the endogenous period of BTBR mice. Starting on postnatal day 90-110, mice underwent a battery of anxiety screens (open field, LD box, elevated plus maze) or a spatial navigation task (Morris water maze) to assess how mild circadian disruption impacts learning and anxiety-like behavior in these strains. Mice raised in a LD cycle that was mismatched from their endogenous rhythm (LD22.75 for C57BL/6 and LD24 for BTBR) displayed more anxiety-like behavior during the open field test and the LD box test and more impulsive behavior during the elevated plus maze. While both disrupted mice and controls showed evidence of learning during the Morris water maze during training, disrupted female mice did not show significant improvements between day 1 and 5 of training, and disrupted mice spent less time in the target quadrant on the probe day. This shows that even a mild form of circadian disruption throughout the lifespan is sufficient to elicit deficits in learning and memory and increased anxiety-like behavior in mice. While circadian disruption in humans may be confounded with other factors, such as diet and socioeconomic status, this study demonstrates that mild circadian disruption alone can alter cognitive and psychological functioning in mice.