Contribution of prefrontal cortex and ventral hippocampus to anxiety in young epileptic mice

Children with epilepsy are particularly vulnerable to anxiety disorders, where these disorders are frequently underdiagnosed and untreated. Despite the high prevalence of anxiety in epilepsy, the underlying neurobiological mechanisms are not fully understood. The medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC) are key brain regions implicated in the genesis and modulation of anxiety, and their interactions play a crucial role in emotional processing including anxiety. We utilized a pilocarpine-induced epilepsy model in young mice (7 weeks old) to assess anxiety-like behaviors using the open field test (OFT), light/dark box, and elevated plus maze (EPM). Local field potential (LFP) recordings were conducted to examine theta power and coherence between the mPFC and vHPC. LFP recordings revealed significantly altered theta power variation in both the mPFC and vHPC during exposure to anxiogenic contexts, suggesting the involvement of these regions in anxiety in the young epileptic mice. Notably, theta-frequency synchrony between the mPFC and vHPC was not significantly altered in the young epileptic mice, indicating that altered theta power rather than inter-regional synchrony may underlie anxiety behaviors in young epileptic mice. Furthermore, we demonstrated that chemogenetic inhibition of excitatory neurons in the mPFC and vHPC reduced anxiety levels in young epileptic mice. Altogether, our findings highlight the critical contributions of mPFC and vHPC to the pathogenesis of comorbid anxiety in epilepsy. These findings underscore the potential therapeutic significance of modulating the activity in these two regions as means to alleviate anxiety in a youth epilepsy population. • Young mice with pilocarpine-induced epilepsy display higher anxiety-like behaviors. • MPFC theta power variation increases in young epileptic mice in anxiogenic contexts. • VHPC theta power variation increases in young epileptic mice in anxiogenic contexts. • Inhibition of mPFC and vHPC reduces anxiety levels in young epileptic mice.