Chronobiometry of behavioral activity in the Ts65Dn model of Down syndrome

Disruption of the sleep-wake cycle has been reported among individuals with Down syndrome (DS). Here we studied behavioral rhythms in adult male and female Ts65Dn mice, a model of DS. The overall behavioral activity of Ts65Dn and diploid (2N) littermates as defined by total movements (TM), movement time (MT), ambulatory movement time (AMT), time spent in center of arena (CT), jumps (JFP), rotational behavior (TURNS), and wheel-running activity (WRA) was recorded under a 12 h:12 h light-dark photocycle. During the light phase, Ts65Dn mice exhibited higher TM, MT, CT, JFP, and WRA compared to 2N littermates. During the dark phase, Ts65Dn and 2N mice differed only in CT and WRA, with the Ts65Dn group engaging in higher levels of both. There were no gender differences for any of the behavioral variables studied. Non-linear least-squares (Cosinor) analysis of the distribution of total behavioral activity (TM) indicated that Ts65Dn mice exhibited a slightly higher mean oscillation (i.e., mesor), but significantly lower amplitude in comparison to 2N mice, suggesting that levels of TM were elevated in trisomic mice but were relatively constant throughout the photocycle. The peak of the Ts65Dn TM rhythm was significantly phase-advanced, occurring approximately 4 h earlier than 2N mice. Overall, Ts65Dn mice were hyperactive and differed significantly in daily patterns of specific behaviors from those of 2N littermates. To control for the potential confound of retinal degeneration in Ts65Dn and 2N mice, we compared and found no difference between the TM rhythm parameters of 2N and non-retinally degenerate C57/129Sv mice, suggesting that abnormal behavioral rhythmicity in Ts65Dn mice may not due to the absence of rod and cone photoreceptors. These results serve as a starting point for further investigations into the physiological basis of sleep-wake disturbances in DS patients.