Environmental Enrichment Has Age- and Sex-Specific Effects on Fear Regulation in Mice

Previous research has sought to understand the mechanisms by which early life adversity disrupts later behavioral function. Yet less has been done to investigate the effects of positive experiences such as environmental enrichment. Here, we examined the effects of brief (2 weeks) or extended (8 weeks) environmental enrichment on discrimination, fear inhibition, and fear extinction during adolescence or adulthood. Two conditions of enrichment were used: a "Hut" group received a polycarbonate Hut in the home cage throughout the duration of the experiment, while a "Variable" group received a polycarbonate Hut, as well as a series of rotating enrichment features. Our data show that in females, brief Variable enrichment increased the rate of learning about cues that explicitly indicate safety during adolescence while disrupting this type of learning in adults. In males, enrichment did not influence learning about safety cues. Conversely, in males, brief Variable enrichment initially improved extinction, but extended enrichment (Variable or Hut) was necessary to see sustained improvements across extinction. This pattern was apparent for both adolescents and adults. In females, Variable enrichment did not affect extinction, while Hut enrichment increased freezing for all mice initially and adolescents as extinction continued. This work has the potential to inform treatments and interventions for fear-related disorders, such as anxiety and post-traumatic stress disorder, tailored for both specific developmental ages and sex.