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Molecular mechanism establishing the OFF pathway in vision
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Journal Article
Molecular mechanism establishing the OFF pathway in vision
2025
Overview
Parallel ON and OFF (positive- and negative-contrast) pathways fundamental to vision arise at the complex synapse of cone photoreceptors. Cone pedicles form spatially segregated functionally opposite connections with ON and OFF bipolar cells. Here, we discover that mammalian cones express LRFN2, a cell-adhesion molecule, which localizes to the pedicle base. LRFN2 stabilizes basal contacts between cone pedicles and OFF bipolar cell dendrites to guide pathway-specific partner choices, encompassing multiple cell types. In addition, LRFN2 trans-synaptically organizes glutamate receptor clusters, determining the contrast preferences of the OFF pathway. ON and OFF pathways converge in the inner retina to regulate bipolar cell outputs. We analyze LRFN2’s contributions to ON-OFF interactions, pathway asymmetries, and neural and behavioral responses to approaching predators. Our results reveal that LRFN2 controls the formation of the OFF pathway in vision, supports parallel processing in a single synapse, and shapes contrast coding and the detection of visual threats.
LRFN2 in cone photoreceptors is vital for building the OFF pathway. Here authors report this cell-adhesion molecule stabilizes contacts with OFF bipolar cells, clusters their ionotropic receptors, and is required for negative-contrast vision and predator-detection behaviors.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14
/ 14/69
/ 38
/ 38/77
/ 64
/ 64/60
/ 9/74
/ Adhesion
/ Animals
/ Cell Adhesion Molecules - genetics
/ Cell Adhesion Molecules - metabolism
/ Clusters
/ Cones
/ Humanities and Social Sciences
/ Humans
/ Mice
/ Receptors, Glutamate - metabolism
/ Retinal Bipolar Cells - metabolism
/ Retinal Bipolar Cells - physiology
/ Retinal Cone Photoreceptor Cells - metabolism
/ Retinal Cone Photoreceptor Cells - physiology
/ Science
/ Vision
