Comparison of Enriched Housing Conditions on Automated Activity Monitoring and Behavior Following Repeated Mild Traumatic Brain Injury in Female C57BL/6 Mice

Abstract

Background: Physical enrichment (PE) and social enrichment (SE) in preclinical studies can improve cognitive health under normal and pathological conditions such as traumatic brain injury. PE includes components such as running wheels, while SE comprises large living areas with multiple cage-mates that promote complex social interactions. Methods: Female C57BL/6J mice were randomly assigned to the automated mouse IntelliCage (SE) or to single-housed Scurry mouse wheel activity cages (PE) and continuously monitored throughout the duration of the study to assess spontaneous and circadian activity. Three weeks after acclimation, mice received sham or rmTBI. One month later, mice underwent behavioral testing using the open field, light/dark box, elevated plus maze, contextual fear conditioning and the Barnes maze to compare potential differences in types of enrichment. Results: A significant main effect of rmTBI was observed on acute measures of spontaneous home-cage activity, with PE mice recovering to baseline levels more quickly. Under both enrichment conditions, rmTBI significantly increased time spent in the light chamber and open arms, decreased contextual fear memory, but did not alter spatial learning. Monitoring continuous activity across the light cycle revealed no effect of rmTBI or enrichment type on circadian rhythm. Conclusion: PE and SE housing environments were comparable in terms of influencing behavioral outcomes following rmTBI in female mice. While PE resulted in a more rapid rate of recovery in activity levels in the acute phase, social isolation is likely to have negative effects over the long-term. Thus, automated monitoring in SE conditions may provide a more translationally relevant and standardized approach to conduct preclinical TBI research. Funding Information: This work was supported by a Department of Veterans Affairs (VA) Rehabilitation Research and Development Merit Review Award 5I01RX002335 (RCK) and the VISN6 Mid-Atlantic Mental Illness Research, Education and Clinical Center. Declaration of Interests: None. Ethics Approval Statement: All procedures described herein were approved by the Durham VAMC IACUC.