Early-life seizures (ELS) often leads to the development of epilepsy (epileptogenesis) in humans, but the underlying mechanisms are unclear. Zebrafish have emerged as a valuable model to study ELS, but whether ELS leads to epileptogenesis in zebrafish is unknown. To address this, we investigated whether ELS in larval zebrafish increases seizure susceptibility later in life.

We induced ELS using the chemoconvulsant pentylenetetrazole (PTZ) daily from 5-7 dpf (days post-fertilization) for 40 minutes. Based on human and rodent ELS studies, we hypothesized that seizure susceptibility would increase compared to controls two weeks after initial seizure induction. Thus, at 21 dpf, we challenged fish with a second dose of PTZ (1, 2.5, or 5 mM) for 20 minutes. We compared the PTZ response in ELS PTZ-exposed (PE) fish to that of handled (HC) and unhandled controls (UC) that did not experience ELS. Outcome measures included latency to first seizure, number of seizures, distance moved, and frequency of high-speed movements.

We found no significant changes between experimental groups possibly due to high variability and low n. However, zebrafish had more seizures as PTZ concentration increased, as expected. The lowest PTZ concentration (1mM) showed the most potential, as the UC fish did not have seizures, but the PE and HC groups did. There was no significant difference in number of seizures or latency to seizures within groups, although it was often lower in PE fish compared to HC fish. At 1mM, the PE group traveled slightly more than the UC and HC groups with more high-speed movement, but again did not reach statistical significance.

Despite the lack of statistical significance, the data is promising. Future experiments will increase the sample size to provide enough statistical power to determine if the zebrafish ELS model can be used to study mechanisms of epileptogenesis.