CONTROL OF WILDTYPE ZEBRAFISH OPTOMOTOR RESPONSE WITH A PHOTOSWITCHABLE DRUG

For animals to interact effectively with their environment, the brain must integrate sensory information and generate appropriate motor responses. Multiple neuronal circuits contribute to this process, and identifying their roles remains a central focus in neuroscience.
The recently developed photoswitchable compound Carbadiazocine controls neuronal firing, modulates zebrafish larval locomotion, and alleviates neuropathic pain in rodents in a reversible, light-induced manner. Given its effects on both motor and somatosensory circuits, we investigated the impact of Carbadiazocine on sensorimotor behaviors, focusing on the optomotor response in zebrafish larvae, and assessed its potential as a tool for circuit perturbation and behavioral analysis.
We performed experiments in head-fixed and free-swimming larvae to assess their capacity to detect and follow the direction of visual stimuli, and to characterize swimming speed patterns and individual tail bout properties following administration of Carbadiazocine photoisomers. In both paradigms, treatment with the pre-illuminated compound induced a marked decrease in accuracy in responding to visual stimuli (correctness dropping from 95% to 70% and from 68% to 20%, respectively). Speed analysis revealed an increased number and duration of fast movements accompanied by a decrease in the count and length of slow movements, even during periods without visual stimulation. Tail bout analysis further showed an increase in 15–30 Hz bout frequencies, corresponding to incomplete, erratic tail movements. All these effects were absent when the dark-relaxed compound was administered.
Together, these findings deepen our understanding of sensorimotor transformations and highlight Carbadiazocine as a spatiotemporally controllable tool for probing neuronal circuits underlying behavior.