SIDEKICK 2 DIRECTS FORMATION OF A RETINAL CIRCUIT THAT DETECTS DIFFERENTIAL MOTION

Abstract

In the mammalian retina, processes of ~70 types of interneurons form specific synapses on ~30 types of retinal ganglion cells (RGCs) in a neuropil called the inner plexiform layer (IPL). Each RGC type extracts salient features from visual input, which are sent deeper into the brain for further processing 1-4. The specificity and stereotypy of synapses formed in the IPL account for the feature-detecting ability of the RGCs. Here, we analyze the development and function of synapses on one RGC type, the W3B-RGC5,6. These cells have the remarkable property of responding when the timing of a small object's movement differs from that of the background, but not when they coincide6. Such cells, called “local edge detectors” or “object motion sensors”, can distinguish moving objects from a visual scene that is also moving6-12. We show that W3B-RGCs receive strong and selective input from an unusual excitatory amacrine cell type called VG3-AC. Both W3B-RGCs and VG3-ACs express the immunoglobulin superfamily recognition molecule Sidekick-2 (Sdk2)13,14, and both loss- and gain-of function studies indicate that Sdk2-dependent homophilic interactions are necessary for the selectivity of the connection. The Sdk2-specified synapse is essential for visual responses of W3B-RGCs: whereas bipolar cells relay visual input directly to most RGCs, the W3B-RGCs receive much of their input indirectly, via the VG3-ACs. This non-canonical circuit introduces a delay into the pathway from photoreceptors in the center of the receptive field to W3B-RGCs, which could improve their ability to judge the synchrony of local and global motion.