Lrrn-mediated retinal ganglion cell targeting drives visual circuit assembly for brightness and contrast detection

Abstract

Brightness and contrast are fundamental features of vision, crucial for object detection, environmental navigation, and feeding. Here, we identify a brightness- and contrast-processing circuit in the zebrafish visual system and uncover the role of leucine-rich repeat neuronal (Lrrn) cell adhesion molecules (CAMs) in regulating its assembly. We show that deep-projecting retinal ganglion cells serve as the first synaptic relay to the brain, requiring Lrrn2 and Lrrn3a for precise axonal targeting within the optic tectum. Using a new reporter line, we achieved high-resolution mapping of this previously undercharacterized vertebrate visual circuit. Genetic disruption of Lrrn CAMs leads to disorganization of the circuit and impairments in brightness and contrast sensitivity, resulting in deficits in visually guided behavior. Additionally, ultrastructural circuit reconstruction and functional imaging analysis identified both its synaptic partners and revealed its critical role in luminance processing. These studies define a core visual processing pathway and establish Lrrn CAMs as essential molecular drivers of its assembly.