Early deficits in social behavior and cortical rhythms in pilocarpine-induced mouse model of temporal lobe epilepsy

Abstract

Many patients with epilepsy are afflicted with psychiatric comorbidities including social dysfunction. However, although social deficits have been a major concern in epilepsy treatment, the relationship between social behavioral pathogenesis and the time course of epileptogenesis is not well defined. To address this, we investigated social behavioral alterations and cortical rhythms during two distinct periods in a mouse model of temporal lobe epilepsy (TLE): 1) a seizure-free, latent period after status epilepticus and 2) the subsequent, chronic period characterized by spontaneous recurrent seizures (SRSs). We found that severe social impairments, such as reduced sociability/social novelty preference, social interaction, social learning, and enhanced defensiveness, appeared during the latent period in mice with TLE. The social dysfunctions in the latent-period mice were nearly comparable to those in the chronic-period mice. We also found that both the latent- and chronic-period mice showed similar aberrant neural activities. They showed enhanced delta-band (1–4Hz) activity and reduced alpha- (8.5–12Hz) and gamma-band (30–55Hz) activity during baseline behavior. Interestingly, concomitant increases in alpha- and gamma-band activities during social behavior, which were characteristic in control mice, were not observed in either latent- or chronic-period mice. Our results indicate that social deficits and abnormal neural activities appear at an earlier stage in epileptogenesis regardless of SRS occurrence. These findings may help to understand behavioral pathogenesis in patients with TLE and at-risk patients with initial insults that develop into TLE.