Scope labchart reader download plus#

Here, we apply one such home-cage monitoring platform 12, 19- 21 to visualize the extent and severity of behavioral impairment in Stargazer mutant mice 22. 12- 15 In this new paradigm, prolonged experimenter-free home-cage recordings minimize observer effects 16, 17, and automated data collection enables computational phenotypes that can be appraised and compared without anthropomorphization. 11 A growing movement seeks to adjunct these assays with naturalistic, continuous and unbiased assessments of spontaneous self-motivated behavior that can be analyzed across multiple time scales. While enormously popular, these tests produce snapshots of behavior in singular readouts that may be amplified/attenuated by arena novelty, and which may be contaminated by variations in motor drive (e.g., hyperactivity) or function (e.g., ataxia).

Scope labchart reader download plus#

Today’s most exciting mouse models often remain subject to a battery of maze- or arena-based assays (e.g., open field test, elevated plus maze, etc.) 8- 10. In contrast, preclinical endpoints to ascertain neurobehavioral impairment have not experienced similar technical or conceptual innovations. With advances in mouse genome engineering, patient-informed genetic DEE mouse models now play a dominant role in devising precision genetic treatments, informed by the latest advances in transcriptomics, neuroimaging and neurophysiology 5- 7. 2, 3 Behavioral comorbidities in particular amplify the risk of psychiatric side effects to antiseizure medications 4, and compound polypharmacy through concurrent prescriptions for neuroleptics, psychostimulants and/or sedatives. In patients with developmental and/or epileptic encephalopathies (DEEs/EEs) 1, seizures and static intellectual disability are often accompanied by motor impairments (quadriparesis, ataxia), disturbances in sleep/arousal, sensory integration, feeding and emotional lability. These findings expand our understanding of the function of Cacng2/CACNG2, variants in which have been identified in patients with bipolar disorder and schizophrenia. 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. Mutants also display an attenuated response to visual and auditory home-cage perturbations, together with profound reductions in voluntary wheel-running. While feeding rhythms, circadian or ultradian oscillations in activity are unchanged, mutants exhibit fragmented sleep bouts, atypical licking dynamics and lowered sucrose preference. We find that despite their gait ataxia, stargazer mutants display horizontal hyperactivity and variable rates of repetitive circling behavior. Here, we combine videotracking and instrumented home-cage monitoring to resolve the neurobehavioral facets of the murine Stargazer syndrome. In the Stargazer mutant mouse, genetic disruptions of Cacng2 result in absence-like spike-wave seizures, cerebellar gait ataxia and vestibular dysfunction.

In many childhood-onset genetic epilepsies, seizures are accompanied by neurobehavioral impairments and motor disability.