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.
Highlights
Seizures are defined as periods of excessive or hyper-synchronous brain activity (Fisher et al., 2014a) which, when recurrent and unprovoked, define the chronic disease epilepsy (Falco-Walter et al, 2018)
These data provide further insight into the electrophysiological characteristics of seizures generated in non-mammalian species by the action of neuroactive drugs
The data we present show that exposure to chlorpromazine, donepezil, picrotoxin and RST results in quantifiable, concentration-dependent, altered neuronal electrophysiology
Summary
Seizures are defined as periods of excessive or hyper-synchronous brain activity (Fisher et al., 2014a) which, when recurrent and unprovoked, define the chronic disease epilepsy (Falco-Walter et al, 2018). Seizures themselves can be definitively identified in human patients and non-clinical animal models using neurophysiological assessment techniques such as local field potential (LFP) recordings and electroencephalography (EEG) (Lévesque and Avoli, 2019; Usman et al, 2019). Using these techniques, seizures can be observed to present diverse electrographic dynamics, with some common components including low voltage fast activity, e.g. high frequency oscillations (HFOs) (Jiménez-Jiménez et al, 2015; Wang et al, 2020) in the fast ripple frequency bands (250-500 Hz), or high amplitude periodic spikes (Jiménez-Jiménez et al, 2015; Perucca et al, 2014; Wang et al, 2020). Precisely how, and where, they are manifest can vary between different forms of epilepsy and different causes of seizure (Jiménez-Jiménez et al, 2015; Perucca et al, 2014; Wang et al, 2020)
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