Rest-activity patterns across development in two mouse models of autism and epilepsy

Sleep disturbances are common in individuals with autism spectrum disorder (ASD) and epilepsy and are increasingly recognized as comorbidities that affect disease severity and quality of life. This study investigated rest-activity patterns across development in two genetic mouse models relevant to ASD and epilepsy: synapsin 2 (Syn2) and contactin-associated protein-like 2 (Cntnap2) knockout (KO) mice, in which epileptic seizures typically emerge at 2-3 months and around 6 months of age, respectively.

Actigraphy, a noninvasive method for monitoring rest-locomotor activity patterns, was performed in male and female Syn2 KO (n = 25), Cntnap2 KO (n = 32), and wild type (n = 31) mice at 1-2, 3-5, and 5-7 months of age. Recordings consisted of 72 h of continuous monitoring during a 12-h light/12-h dark cycle following a 12-h acclimatization period. Infrared sensors at two cage heights detected both subtle and prominent movements, allowing analysis of age-dependent rest-activity rhythms.

Across all genotypes and ages, mice showed higher activity during the dark phase, confirming the light phase as the preferred rest/sleep period. Adolescent (1-2 months) Syn2 KO mice exhibited normal rest-activity patterns, whereas adult (3-5 months) Syn2 KO mice displayed increased activity during the dark phase. In contrast, no robust age-dependent rest-activity alterations were detected in either adolescent or adult Cntnap2 KO mice after correction for multiple comparisons.

Adult Syn2 KO mice exhibit hyperactivity during their preferred wake period, coinciding with the age range associated with seizure emergence in this model, whereas Cntnap2 KO mice do not exhibit robust developmental alterations in rest-activity behavior. These findings highlight genotype- and age-dependent differences in mouse models relevant to ASD and epilepsy.

Sleep problems are common in people with autism and epilepsy, but why they occur is still unclear. In this study, we examined rest-activity patterns in mice carrying two different genes linked to autism and epilepsy using a noninvasive method that tracks movement over time. We found that mice lacking the Syn2 gene developed hyperactivity in adulthood, during a life stage associated with seizures in this model, whereas mice lacking the Cntnap2 gene did not show consistent changes in rest-activity patterns across development. These findings suggest that activity patterns in genetic models of autism and epilepsy depend on age and genetic background.