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

Abstract

We assessed similarities and differences in the electrographic signatures of local field potentials (LFPs) 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. LFPs were recorded from the midbrain of 4-d-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 LFPs, 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 nonmammalian species by the action of neuroactive drugs.