Effects of Environmental Enrichment on Autism-Related Behaviors in the BTBR T+Tf/J Mouse

Background:  Some core features of autism have been identified in the BTBR mouse including social deficits and repetitive and stereotyped behaviors.  In addition, sensory processing differences and anxiety-like behaviors have been reported in this mouse model. In humans, amelioration of some autism-related behaviors has been reported using sensory integration treatments which share core features of the animal sensory-enrichment paradigm. To date, no studies have looked at the effects of environmental enrichment on autism-related behaviors in the BTBR mouse. Therefore, the purpose of this study was to see if environmental enrichment influenced the development of social deficits, repetitive behaviors, exploratory behavior, and sensory responsivity in the BTBR mouse model of autism.

Objectives:  1) Examine differences in autism-related behaviors between BTBR and control (B6) mice at baseline (7-8 weeks) to expand upon and replicate previous studies using this animal model; 2) Compare changes in autism-related behaviors in BTBR mice following 30 days in either an enriched or standard housing condition.

Methods:  Thirty one mice were divided into one of four experimental groups: Control Enriched (8), Control Standard (8), BTBR Enriched (8), and BTBR Standard (7). Baseline testing was done between 7-8 weeks of age; upon completion of this testing mice were placed in either enriched or standard housing for thirty days. The enriched housing cage was a large dog kennel divided into three levels with wire mesh. Novel items were placed in the enriched cage every 5 days.  At the end of the 30 days, post-testing was conducted. The following behavioral tests were conducted at pre-test and post-test: Auditory and Tactile Startle Responsivity, Open Field, Socialization (3-chambered apparatus), Lower Order Repetitive Behavior (LRB) and Higher Order Repetitive Behavior (HRB) paradigms. The LRB paradigm focused on the animal’s repetitive grooming behavior while the HRB paradigm examined patterns of object exploration.

Results:  At pretest BTBR mice showed no differences in socialization compared to the B6 controls, however they groomed significantly more often, showed diminished auditory and tactile startle responses, and showed less exploratory behavior in the open field.  At post-test BTBR mice housed in the enriched condition spent significantly more time engaged in social sniffing of a novel mouse and significantly less time grooming (LRB) compared to BTBR mice housed in standard condition. Enriched BTBR mice also showed a trend towards increased exploratory behavior in the open field, while BTBR mice housed in a standard condition showed a significant decrease in exploratory behavior at post-test.

Conclusions:  Similar to previous authors, we found that BTBR mice exhibit autistic-like behaviors including high rates of repetitive grooming. Unlike previous reports, we did not find these animals to be hypersensitive to tactile stimuli, nor did we see differences in social behavior at baseline. Our results suggest that environmental enrichment may be beneficial in reducing lower-order repetitive behaviors, increasing social interaction, and increasing exploratory behavior in this animal model; findings may help guide outcomes research for children with autism using sensory integration treatment.