Modulation of the zebrafish optokinetic reflex by pharmacologic agents targeting GABA_A receptors

Optokinetic reflex (OKR) responses provide a convenient means to evaluate visual, integrative and oculomotor function in larval zebrafish. We measured multiple aspects of the OKR response in zebrafish exposed systemically to compounds altering signaling at GABA_A receptors in order to derive quantitative concentration-response relationships. The GABA_A antagonist picrotoxin caused concentration-dependent decreases in reflex gain, saccade velocity, saccade amplitude, interocular concordance and interocular gain. Conversely, the GABA_A agonist gaboxadol provoked increases in reflex gain, saccade velocity, saccade amplitude and ocular range at low concentrations, and decreases in some of these parameters at higher concentrations. These data show that GABA_A signaling influences multiple aspects of the OKR (including gain, generation of saccades, and coordination between the two eyes) and provide proof of concept that quantitative OKR analysis can be used as a tool for chemical biology and neuropharmacology applications.