Home-cage behavior in the Stargazer mutant mouse

Abstract

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.

Bouts of rest and physical activity in C57BL/6J mice

“…As expected, few occurs during lights on because mice are nocturnal. The typical locomotor bout covers a distance of 0.1-0.2 m with a speed of ∼3 cm s -1 , which agrees with previously published data recorded with DVC and other types of HCM systems[53, 56, 59, 60] but lower than those reported by [44, 45]. This discrepancy in average speed may relate to differences in the definition of a locomotor bout (speed or distance).…”

“…, which agrees with previously published data recorded with DVC and other types of HCM systems [53,56,59,60] but lower than those reported by [44,45]. This discrepancy in average speed may relate to differences in the definition of a locomotor bout (speed or distance).…”

“…The results of these studies show a correlation >0.9 between NREM and REM sleep, on the hand, and the animals being still ≥40s, on the other. This behavioural criterion for sleep has subsequently been used in a number of studies [51][52][53][54][55]. We conclude based on our results and those obtained with other HCM techniques (idem) that bouts of inferred sleep (no distinction made here between NREM and REM) in single housed mice of this strain commonly have a duration of 300-400s but can exceed 1000s and occur with an average density of ~120 bouts per day preferentially during lights on.…”

“…With GPS tracking becoming a more frequent feature of wearable devices also distance made and speedograms will be possible to retrieve as indices. Similarly, data generated by a variety of HCM systems have recently been used in efforts to identify behavioural indices of ageing[29, 83], impact of disease progression[42, 43, 60, 84, 85], genetic modification[44, 48, 51, 53, 86], and insults[59, 60, 87].…”

Actigraphic Correlates of Neuropsychiatric Disability in Adult Patients with Focal Epilepsy

“…With the increasing popularity of continuous, in situ , digital phenotyping tools in human subject research, prolonged continuous behavioral assessments of rodent or zebrafish models can now be seamlessly obtained through solutions that employ automated video tracking within the home-cage/-tank 29,78 . These technologies have been successfully employed to measure the severity of post-ictal locomotor suppression 79 , locomotor profiles associated with ASM exposure 80,81 and model-specific distortions in rest/activity rhythms 82,83 . Importantly, such preclinical platforms can elaborate the locomotor consequences of ASM exposure in animals without epilepsy , while simultaneously assessing RARs in spontaneously seizing animal subjects in the absence of ASM exposure, thereby providing a fertile substrate to directly test causal hypotheses derived from human subject studies.…”