Automated home-cage assessment in SOD1 mice uncovers early sex-dependent deficits in voluntary wheel running and cognitive timing ability

Motor and cognitive ability evaluations are crucial in assessing mouse models of neurodegenerative disease. We recently validated automated home-cage based running-wheel and interval timing tasks (TSE Systems) that enable continuous monitoring of motor and cognitive performance without handler interference, features that are desirable in longitudinal studies. To study how deficits vary with respect to sex, age of onset, rate of progression and severity of symptoms, we investigated these parameters in a genetic model of Amyotrophic Lateral Sclerosis (ALS), Tg(SOD1G93A)dl1/GurJ (SOD1). We challenged male and female mice of different ages on one or multiple 3-weeks sessions to verify the effect of voluntary wheel running on the disease progression, motor function and survival. Male and female SOD1 mice differed in survival and disease progression depending on wheel running experience. Repeated 3-weeks wheel running sessions improved motor function but shortened survival in male SOD1 mutant mice. SOD1 mutants were also tested in an automated home-cage apparatus to evaluate cognitive timing ability and its circadian regulation. Error rate at discrete time points across the light-dark cycle was altered in mutants as was their ability to discriminate between short and long intervals. Females showed greater impairments than males. Wheel-running and cognitive difficulties were observed in SOD1 mutants earlier than those detected using conventional tasks, such as the Rotarod, making these home-cage automated systems reliable tools to uncover deficits at pre-symptomatic stages in models of neurodegenerative disease.