A dedicated retina-EmT-habenula pathway controls light preference of larval zebrafish

Baibing Zhang:1,2 Yuanyuan Yao:1,2 Koichi Kawakami:4 Marnie E. Halpern:5 Jiulin Du:1,2,3 
(1:Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences 2:School, University of Chinese Academy of Sciences, Shanghai, China 3:School of Life Science and Technology, ShanghaiTech University, Shanghai, China 4:Division of Molecular and Developmental Biology, National Institute of Genetics, Shizuoka, Japan 5:Department of Embryology, Carnegie Institution for Science, Department of Biology, Johns Hopkins University, Baltimore, MD)

Appropriate preference for light or dark is crucial for animal survival. However, the underlying neural circuit mechanism remains unclear especially for vertebrates. Here, integrating behavioral assay, in vivo opto- and electro-physiological recordings, optogenetics and morphological tracing in larval zebrafish, we found that a circuitry consisting of retinal ganglion cells (RGCs), eminentia thalamus (EmT) and left dorsal Habenula (L-dHb) mediates light preference behavior. Lesion or dysfunction of the L-dHb diminished retina-dependent light preference, while optogenetic activation of the L-dHb endowed eye-removing zebrafish with light preference. L-dHb neurons can code background luminance, because they exhibit sustained and light intensity-dependent responses to light flashes as long as stimuli last, a property important for light preference behavior. Light preference-associated visual inputs of the L-dHb are conveyed through EmT neurons, which contact the axonal arborization field 4 of RGCs, display sustained light responses, project to the L-dHb, form excitatory synapses with L-dHb neurons, and are required for light preference. Thus, our study identifies a neural circuitry, which underlies light preference in vertebrates, and provides new insights about the function of the EmT and Habenula.