Environmental enrichment and social isolation modulate inhibitory transmission and plasticity in hippocampal area CA2

Environmental factors are well-accepted to play a complex and interdependent role with genetic factors in learning and memory. The goal of this study was to examine how environmental conditions altered synaptic plasticity in hippocampal area CA2. To do this, we housed adult mice for 3 weeks in an enriched environment (EE) consisting of a larger cage with running wheel, and regularly changed toys, tunnels and treats. We then performed whole-cell or extracellular field recordings in hippocampal area CA2 and compared the synaptic plasticity from EE-housed mice with slices from littermate controls housed in standard environment (SE). We found that the inhibitory transmission recruited by CA3 input stimulation in CA2 was significantly less plastic in EE conditions as compared to SE following an electrical tetanus. We demonstrate that delta-opioid receptor (DOR) mediated plasticity is reduced in EE conditions by direct application of DOR agonist. We show that in EE conditions the overall levels of GABA transmission is reduced in CA2 cells by analyzing inhibition of ErbB4 receptor, spontaneous inhibitory currents and paired-pulse ratio. Furthermore, we report that the effect of EE of synaptic plasticity can be rapidly reversed by social isolation. These results demonstrate how the neurons in hippocampal area CA2 are sensitive to environment and may lead to promising therapeutic targets.

Automated summary

This study aimed to investigate the impact of environmental conditions on synaptic plasticity in the hippocampal area CA2. The research found that inhibitory transmission in the CA2 region of mice housed in an enriched environment was less plastic compared to mice housed in a standard environment. The study also showed that delta-opioid receptor-mediated plasticity was reduced in enriched environment conditions, and overall levels of GABA transmission were decreased. Additionally, the effect of the environment on synaptic plasticity could be rapidly reversed by social isolation.