Abstracts

Rationale: The zebrafish model is an emerging tool in experimental epilepsy. Zebrafish larvae, in particular, are advantageous as disease models because they can be easily genetically altered and can be used for developmental and drug studies where agents applied to the bath penetrate the organism easily. Yet, methods to perform noninvasive brain electrophysiological recordings in zebra fish are limited. We present a novel method, using multi-electrode array recordings, to simultaneously record electrical activity from up to 61 cranial locations of an intact larval zebra fish without penetrating to the intracranial space. This method enables recording of single unit activity and EEG signal. Methods: We recorded spontaneous brain single unit activity from zebrafish larva (n=4) by placing the dorsal side of each larva-head onto a microelectrode array (MED64 system) during continuous flow of oxygenated artificial cerebrospinal fluid (aCSF). Results: Recording of spontaneous activity was possible for at least three hours. Spike frequency and continuous or bursting pattern at individual electrode locations were reliably recorded. Following 25 mM KCl infusion into the aCSF, spike frequency and burst frequency increased significantly in all fish. Average spike frequency in particular increased by a factor of 1.8 (p<0.02), thus nearly doubled. In three out of four fish we also found an increase in the number of channels with active firing units after KCl application, thus showing spatial spread of the epileptiform activity. Conclusions: In summary, we recorded single unit activity in vivo from multiple extracranial electrodes positioned on intact larval zebra fish for several hours and documented a seizure-type pattern following exposure to high-concentration of KCl. This high spatial and temporal resolution method complements present zebrafish neurophysilogical techniques and can enable future pharmacological and genetic experiments with this model.