Differential electrographic signatures generated by mechanistically-diverse seizurogenic compounds in the larval zebrafish brain

We assessed similarities and differences in the electrographic signatures of local field potentials evoked by different pharmacological agents in zebrafish larvae. We then compared and contrasted these characteristics with what is known from electrophysiological studies of seizures and epilepsy in mammals, including humans. Ultimately, our aim was to phenotype neurophysiological features of drug-induced seizures in larval zebrafish for expanding knowledge on the translational potential of this valuable alternative to mammalian models. Local field potentials were recorded from the midbrain of 4-day old zebrafish larvae exposed to a pharmacologically diverse panel of seizurogenic compounds, and the outputs of these recordings were assessed using frequency domain analysis. This included analysis of changes occurring within various spectral frequency bands of relevance to mammalian CNS circuit pathophysiology. From these analyses, there were clear differences in the frequency spectra of drug-exposed local field potentials, relative to controls, many of which shared notable similarities with the signatures exhibited by mammalian CNS circuits. These similarities included the presence of specific frequency components comparable to those observed in mammalian studies of seizures and epilepsy. Collectively, the data presented provide important information to support the value of larval zebrafish as an alternative model for the study of seizures and epilepsy. These data also provide further insight into the electrophysiological characteristics of seizures generated in non-mammalian species by the action of neuroactive drugs.Significance StatementIn this study we offer novel insight into the frequency domain of the local field potentials (LFPs) for a range of seizurogenic compounds in zebrafish larvae. We make a direct comparison of seizurogenic compounds with varying mechanisms of action and, where possible, compare the effects of these compounds in zebrafish larvae with those recorded in mammals in terms of the frequency components of their LFPs. This study adds to the mounting body of evidence supporting the use of the larval zebrafish as a powerful alternative model organism for seizure and epilepsy research.