Abstracts

Rationale: Cortical spike-wave-discharges (SWDs) with behavioral arrest are an established model of human absence (genetic) seizures in inbred rat strains. However, these epileptiform events are also commonly observed in healthy outbred strains, suggesting either that many normal control rats used in scientific studies have absence epilepsy or that SWDs in these animals are not epileptic events. We hypothesized that SWD events in outbred rats are not absence seizures associated with behavioral arrest, but are a normal and voluntary behavior. A central prediction of this hypothesis is that rats are aware of and can control SWD behavior, and here we report the first controlled test of this prediction using a simple operant learning paradigm. Methods: The EEGs of 5 Sprague-Dawley rats (9-12 mo) were recorded from parietal cortical electrodes. Pattern recognition was used to detect the occurrence of SWDs in real time. Rats were rewarded with a sugar pellet 2 s after completing each SWD burst. Thirty minutes of reward were alternated with 30-min of no reward for 2 sessions/day over 20 days. Results: In no-reward periods, burst-rates were lower (23.4 0.28 bursts/hr) compared to the reward periods (44.3 2.6 bursts/hr; p < .001). Most of the increase during the period with rewards was due to shorter (3-5 sec) SWD bursts, where the average duration shortened from 8.3 0.27 sec during no-reward to 5.5 0.21 sec during reward (p < .001). Thus, rats produced more bursts of shorter duration to receive the reward. During reward, rats also actively checked the pellet tube (detected with a photo-interrupter beam) after completing SWDs but before delivery, demonstrating they were aware of SWD event completion prior to the auditory cue of pellet delivery. Conclusions: Human absence seizures are defined by impairment of consciousness (absence) that is spontaneous and not under voluntary control (seizure). Evidence presented here indicates that rats are aware of - and remember - SWD events and that they use this mechanism as an internal cue to preemptively seek expected reward. Specifically, rats appear to shorten the duration and increase the frequency of SWDs to obtain reward. This observation begs the question: Are SWDs and associated immobility part of the normal rat behavioral repertoire, and not absence seizures. SWDs may not be good models for absence epilepsy. Instead, SWDs may represent the rat equivalent of the human alpha rhythm during relaxed wakefulness. The absence "seizures" of inbred WAGrji rats are currently being examined for similar operant control of SWDs. Funding: Funded by CURE 411446 and CDMRP EP150033