Sinusoidal analysis reveals a non-linear and dopamine-dependent relationship between ambient illumination and motor activity in larval zebrafish.

Larval zebrafish show stereotyped motor responses to changes in ambient illumination. The responses can be evaluated in 96-well plates, and are used widely to assess neurological function in zebrafish models. However, the square-wave (on/off) light stimuli commonly employed in these studies do not allow analysis of the relationship between motor activity and illumination intensity or its rate of change. To address this limitation, we measured larval zebrafish motor function while ambient illumination was modulated sinusoidally. Motor activity varied robustly and reproducibly in antiphase with illumination. The relationship between mean swimming speed (dependent variable) and illuminance (independent variable) was described most closely by a power function, and was influenced dynamically by the proportional rate of change of illuminance. Several predictions from this model were verified experimentally by testing responses to sinusoidal illumination waveforms that were amplitude-, phase-, or offset-modulated, or transformed by a power function. At concentrations ≤5 μM, the dopamine D2 receptor inverse agonist haloperidol selectively abrogated the motor response to decreasing Illuminance without altering baseline activity in bright light, suggesting that dopamine is essential for illuminance-dependent motor function. These data contribute to understanding the environmental determinants of motor activity in zebrafish larvae, suggest experimental opportunities to elucidate underlying neural mechanisms, and potentially provide an assay of dopaminergic function for chemical and genetic screening applications.