Early-life seizures (ELS) can disrupt brain development, often leading to cognitive impairments in humans and rodents. Here, we investigated whether seizures in larval zebrafish (Danio rerio) lead to acute and chronic learning deficits. We hypothesized that seizures in larval zebrafish would impair their performance in declarative memory tasks. To test this, we induced seizures in larval zebrafish using the chemoconvulsant pentylenetetrazole (PTZ). We then assessed later-life learning using short-term memory tasks that focused on conscious recognition and interest in novel stimuli. Specifically, for acute memory (5 days after seizure induction), we used the visual lateralization novel object recognition (VLNOR) test, based on the novel object recognition test frequently used in rodents. Zebrafish show asymmetries in the use of left (LES) and right eye systems (RES), and will initially use LES to observe novel objects and RES to view familiar objects. We found that PTZ fish never reached 50% RES use during the observation phase whereas the UC fish reached 50% RES by 4 minutes. Interestingly, RES behavior patterns of PTZ fish during the recall phase were similar to that of naïve fish during the observation phase. To assess chronic memory deficits, we tested fish in a y-maze spatial learning task 3 months after seizures. In this task, fish had to recall the novel arm of the maze 90 minutes after being removed from the maze. The PTZ group spent significantly less time in the novel arm of the y-maze during the recall test compared to their UC clutchmates. Finally, we have begun preliminary molecular studies which show distinct expression profiles of synaptic plasticity genes between PTZ and control groups by qPCR. These findings expand the behavioral characterization of the larval zebrafish seizure model, strengthening the power of this model for researching the cognitive consequences of ELS.
Available at: http://works.bepress.com/jocelyn-lippman-bell/13/