Study of social behavior in an animal model of atypical absence epilepsy

Abstract

Absence epilepsy is characterized by a distinct spike-and-wave discharge (SWD) in the electroencephalogram (EEG). Unlike the typical form of absence epilepsy, atypical absence epilepsy (AAE) showing slow SWD (<3 Hz) is characterized by severely abnormal cognition and neurodevelopmental or neurological outcomes in humans. Plus, only thalamocortical circuitry is involved in the typical form of absence epilepsy, whereas AAE is known to involve limbic circuitry including hippocampus as well as thalamocortical circuitry. However, despite the severe cognitive and neurodevelopmental outcomes in AAE, the relationship between AAE and social-behavioral dysfunctions has not been defined well, either experimentally or in patients with AAE. In this study, we characterized social behaviors in the mouse model of AAE.AAE in the mouse was induced by repeated postnatal administration of AY-9944 (AY), a cholesterol biosynthesis inhibitor, every 6 days from postnatal day (P) 2 to P20. SWD was investigated in frontal cortex, parietal cortex, and hippocampus by long-term video-EEG monitoring. AY-treated mice performed various social behavior tests such as sociability/social novelty preference, social interaction with a juvenile conspecific, observational fear, and resident-intruder aggression. As a result, AY-treated mice exhibited spontaneous, recurrent, and synchronous SWD. The average frequency of SWD was 4-5 Hz in EEG recordings. Furthermore, AY-treated mice showed behavioral dysfunction in social interactions with a juvenile conspecific, sociability/social novelty preference, and social fear learning tests. AY-treated mice also exhibited increased levels of offensive behaviors in a resident-intruder test. Together, these results suggest abnormal epileptic activity during postnatal development and severely altered social behaviors in AY-9944 model, which may help to reveal neural mechanisms underlying AAE. This study can provide novel and valuable information about brain dise...