Home-cage behavior in the Stargazer mutant mouse

In many childhood-onset genetic epilepsies, seizures are accompanied by neurobehavioral impairments and motor disability. In the Stargazer mutant mouse, genetic disruptions of Cacng2 result in absence-like spike-wave seizures, cerebellar gait ataxia and vestibular dysfunction, which limit traditional approaches to behavioral phenotyping. Here, we combine videotracking and instrumented home-cage monitoring to resolve the neurobehavioral facets of the murine Stargazer syndrome. We find that despite their gait ataxia, stargazer mutants display horizontal hyperactivity and variable rates of repetitive circling behavior. While feeding rhythms, circadian or ultradian oscillations in activity are unchanged, mutants exhibit fragmented bouts of behaviorally defined sleep, atypical licking dynamics and lowered sucrose preference. Mutants also display an attenuated response to visual and auditory home-cage perturbations, together with profound reductions in voluntary wheel-running. Our results reveal that the seizures and ataxia of Stargazer mutants occur in the context of a more pervasive behavioral syndrome with elements of encephalopathy, repetitive behavior and anhedonia. These findings expand our understanding of the function of Cacng2.

Automated summary

In childhood-onset genetic epilepsies, seizures are often accompanied by neurobehavioral impairments and motor disability. By studying the Stargazer mutant mouse, researchers found that disruptions in the Cacng2 gene led to absence-like spike-wave seizures, cerebellar gait ataxia, and vestibular dysfunction. Using video tracking and instrumented home-cage monitoring, they observed that Stargazer mutants exhibited hyperactivity, repetitive circling behavior, fragmented sleep patterns, atypical licking dynamics, decreased sucrose preference, and reduced responses to environmental perturbations. These findings highlight the comprehensive behavioral syndrome associated with Stargazer mutants, providing insights into the function of Cacng2.