Light-preference behavior is a highly conserved innate behavior throughout the animal kingdom and is crucial for animal survival. A recent study published online in Neuron discovered that visual inputs from an asymmetrical pathway in larval zebrafish, comprising of a specific subset of retinal ganglion cells (RGCs), the eminentia thalami (EmT) and the left dorsal Habenula (L-dHb) mediates light-preference behavior. This work is highlighted with a video abstract on the website of Neuron. It was performed by Dr. DU Jiulin’s research group at the Institute of Neuroscience and Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.

　　The Hb is an evolutionarily conserved diencephalic structure in vertebrates. Studies in mammals showed that the Hb plays critical roles in emotion-related behaviors, including anxiety, fear, reward processing and depression, through integrating inputs mainly from the limbic system and basal ganglia. However, the Hb also receives inputs from multiple sensory modalities. The function and underlying neural circuit of Hb sensory inputs remain unknown.

　　To explore the function of Hb’s visual inputs, Dr. Du’s group firstly examined the role of the Hb in light-preference behavior. Normal zebrafish larvae showed robust light-preference behavior, which depended on visual inputs from the eyes. Removing bilateral eyes or silencing RGCs function impaired  light preference markedly. Interestingly, lesion or dysfunction of the L-dHb but not right dorsal Hb (R-dHb) severely impaired retinal input-dependent light-preference behavior, while optogenetic activation of L-dHb neurons endowed eye-removed zebrafish with preference capability, suggesting the Hb is crucial for the light-preference behavior. Then, the researchers performed in vivo whole-cell recording and calcium imaging on Hb neurons and found that visually responsive Hb neurons preferentially located at the L-dHb and their sustained activities and firing frequencies encoded the presence and intensity of ambient light, respectively. Through these two encoding strategies, L-dHb could sense real-time contexture brightness, a prerequisite for mediating light-preference behavior. In order to find out how visual information is relayed to the L-dHb, researchers  then combined morphological tracing and functional assays and found that L-dHb neurons receive excitatory monosynaptic inputs from bilateral EmT, and EmT neurons are contacted mainly by RGCs at the arborization field 4 (AF4) of retinorecipient brain areas. Consistently, dysfunction of the EmT impaired light-preference behavior, suggesting that the RGC - EmT - L-dHb pathway mediates the light-preference behavior. Finally, to elucidate the origin of the asymmetry, they carefully characterized this pathway. The majority of AF4-projecting RGCs were found to locate in the ventral retina and were sustained ON-type cells. The EmT received visual inputs from contralateral RGCs and exhibited sustained and symmetrical visual responses. Importantly, bilateral EmT preferentially innervated the L-dHb but not R-dHb, leading to the asymmetrical visual responses in the L-dHb.

　　This study reveals a novel function of the Hb and for the first time, elucidates the neural circuit mechanism of light-preference behavior in vertebrates. It extends the spectrum of Hb functions to light-preference behavior and suggests that the Hb may act as a node for crosstalk between sensory and emotion systems in the brain.

　　This work entitled “Left Habenula Mediates Light-Preference Behavior in Zebrafish via an Asymmetrical Visual Pathway” was published online in Neuron on February 10 , 2017. It was carried out mainly by ZHANG Baibing and YAO Yuanyuan, with help from Dr. ZHANG Hefei, under the supervision of Dr. DU Jiulin at the Institute of Neuroscience, Chinese Academy of Sciences, and in collaboration with Dr. Koichi Kawakami at National Institute of Genetics, Japan. .

　　Figure legend: Left, an image that is inspired from an artistic conception of an ancient Chinese poetry: “Moonlight over the Lotus Pond”, illustrates moonlight over the lotus pond, and fish swimming towards the bright shadow of the moon. Right, working model showing that the AF4-projecting RGCs – EmT – L-dHb pathway mediates light-preference behavior. A subset of sustained RGCs project to contralateral EmT through the AF4 region, transmitting ambient illuminance information to EmT. And then bilateral EmT preferentially project to L-dHb, relaying the illuminance information asymmetrically to the L-dHb to trigger light-preference behavior.