Early life circadian rhythm disruption in mice alters brain and behavior in adulthood

Abstract

AbstractHealthy sleep supports robust development of the brain and behavior. Modern society presents a host of challenges that can impair and disrupt critical circadian rhythms that reinforce optimal physiological functioning, including the proper timing and consolidation of sleep. While the acute effects of inadequate sleep and disrupted circadian rhythms are being defined, the adverse developmental consequences of disrupted sleep and circadian rhythms are understudied. Here, we exposed mice to disrupting light–dark cycles from birth until weaning and demonstrate that such exposure has adverse impacts on brain and behavior as adults. Mice that experience early-life circadian disruption exhibit more anxiety-like behavior in the elevated plus maze, poorer spatial memory in the Morris Water Maze, and impaired working memory in a delayed match-to-sample task. Additionally, neuron morphology in the amygdala, hippocampus and prefrontal cortex is adversely impacted. Pyramidal cells in these areas had smaller dendritic fields, and pyramidal cells in the prefrontal cortex and hippocampus also exhibited diminished branching orders. Disrupted mice were also hyperactive as adults, but otherwise exhibited no alteration in adult circadian locomotor rhythms. These results highlight that circadian disruption early in life may have long lasting and far-reaching consequences for the development of behavior and the brain.