Environmental Enrichment Rescues Social Behavioral Deficits and Synaptic Abnormalities in <i>Pten</i> Haploinsufficient Mice

• Main Authors: Amy E. Clipperton-Allen, Angela Zhang, Ori S. Cohen, Damon Theron Page
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Genes
• Subjects: environmental enrichment; synaptic plasticity; <i>Pten</i>; autism; neurodevelopment
• Online Access: https://www.mdpi.com/2073-4425/12/9/1366

<i>Pten</i> germline haploinsufficient (<i>Pten</i>^+/−) mice, which model macrocephaly/autism syndrome, show social and repetitive behavior deficits, early brain overgrowth, and cortical–subcortical hyperconnectivity. Previous work indicated that altered neuronal connectivity may be a substrate for behavioral deficits. We hypothesized that exposing <i>Pten</i>^+/− mice to environmental enrichment after brain overgrowth has occurred may facilitate adaptation to abnormal “hard-wired” connectivity through enhancing synaptic plasticity. Thus, we reared <i>Pten</i>^+/− mice and their wild-type littermates from weaning under either standard (4–5 mice per standard-sized cage, containing only bedding and nestlet) or enriched (9–10 mice per large-sized cage, containing objects for exploration and a running wheel, plus bedding and nestlet) conditions. Adult mice were tested on social and non-social assays in which <i>Pten</i>^+/− mice display deficits. Environmental enrichment rescued sex-specific deficits in social behavior in <i>Pten</i>^+/− mice and partially rescued increased repetitive behavior in <i>Pten</i>^+/− males. We found that <i>Pten</i>^+/− mice show increased excitatory and decreased inhibitory pre-synaptic proteins; this phenotype was also rescued by environmental enrichment. Together, our results indicate that environmental enrichment can rescue social behavioral deficits in <i>Pten</i>^+/− mice, possibly through normalizing the excitatory synaptic protein abundance.