Left Habenula Mediates Light-Preference Behavior in Zebrafish via an Asymmetrical Visual Pathway.

Habenula (Hb) plays critical roles in emotion-related behaviors through integrating inputs mainly from the limbic system and basal ganglia. However, Hb also receives inputs from multiple sensory modalities. The function and underlying neural circuit of Hb sensory inputs remain unknown. Using larval zebrafish, we found that left dorsal Hb (dHb, a homolog of mammalian medial Hb) mediates light-preference behavior by receiving visual inputs from a specific subset of retinal ganglion cells (RGCs) through eminentia thalami (EmT). Loss- and gain-of-function manipulations showed that left, but not right, dHb activities, which encode environmental illuminance, are necessary and sufficient for light-preference behavior. At circuit level, left dHb neurons receive excitatory monosynaptic inputs from bilateral EmT, and EmT neurons are contacted mainly by sustained ON-type RGCs at the arborization field 4 of retinorecipient brain areas. Our findings discover a previously unidentified asymmetrical visual pathway to left Hb and its function in mediating light-preference behavior. VIDEO ABSTRACT.