Daily rhythms of seizure activity and behavior in a model of atypical absence epilepsy

Abstract

We studied daily rhythms of chronic seizure activity and behavior in adult rats and mice treated with the cholesterol biosynthesis inhibitor AY-9944 (AY) during early postnatal development. Chronic atypical absence seizures were verified in the AY-treated animals by the presence of spontaneous 5- to 6-Hz slow spike–wave discharges (SSWDs) in the neocortex. General behavioral activity, as measured by total movements (TM), movement time (MT), ambulatory movement time (AMT), time spent in center of arena (CT), jumps (JFP), and rotational behavior (TURNS), were continuously recorded under a 12-hour light:12-hour dark photocycle. The average SSWD duration in AY-treated rats varied daily, with two peaks occurring at approximately dark phase and light phase onset. Mice treated with AY exhibited significant increases in all behavioral measures during the light and dark phases, with the exception of light-phase CT, which did not differ from that of controls. Consequently, the daily rhythm of total behavioral activity (TM) exhibited a significantly higher mean oscillation (mesor) and amplitude without evidence of phase shift compared with the TM rhythm of controls. The occurrence of SSWD activity in the AY model appears to be subject to regulation by biological timing mechanisms and, furthermore, associated with motor hyperactivity that does not alter the timing of behavioral rhythmicity.