A dopaminergic visuomotor gateway to the zebrafish optic tectum

Abstract

Dopamine (DA) is widely known as a neuromodulator essential for reward, motivation and learning, yet it also modifies rapid sensorimotor transformations. Understanding how dopaminergic neurons process sensory input and motor-related signals is therefore critical for elucidating their role in sensorimotor control. In vertebrates, a conserved visual center under dopaminergic influence is the superior colliculus, or optic tectum in fish. Here, using anatomical and molecular analyses in larval zebrafish, we identify a defined cluster of pretectal DA (PrDA) neurons whose axons densely innervate the tectum, predominantly in its deep neuropil. Combining functional Ca2+ imaging with visual stimulation and motor recordings, we show that PrDA neurons respond reliably to visual stimulation. However, most PrDA neurons exhibit pronounced activity also during spontaneous locomotion, and enhanced activity when visual stimuli and motor output co-occur, indicating that PrDA neurons integrate convergent input from visual and motor centers. Furthermore, spontaneous PrDA neuron activity was synchronized and the synchrony was even stronger when visual or motor activity contributed to their activation. Notably, as visual stimuli differed in their efficacy to drive swim activity, motor-associated responsiveness of PrDA neurons produced apparent direction selectivity to stimulus motion when motor activity was not accounted for. This apparent neural response bias disappeared once motor activity was taken into account. Together, these findings suggest that PrDA neurons provide rapid, visuomotor-related dopaminergic modulation of tectal circuits that transform visual information into context-dependent motor commands, a principle that may extend to homologous mammalian midbrain circuits.