Sidekick 2 directs formation of a retinal circuit that detects differential motion

In the mammalian retina, processes of approximately 70 types of interneurons form specific synapses on roughly 30 types of retinal ganglion cells (RGCs) in a neuropil called the inner plexiform layer. 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 inner plexiform layer account for the feature-detecting ability of RGCs. Here we analyse the development and function of synapses on one mouse RGC type, called the W3B-RGC(5,6). These cells have the remarkable property of responding when the timing of the movement of a small object differs from that of the background, but not when they coincide(6). Such cells, known as local edge detectors or object motion sensors, can distinguish moving objects from a visual scene that is also moving(6-12). We show that W3B-RGCs receive strong and selective input from an unusual excitatory amacrine cell type known as VG3-AC (vesicular glutamate transporter 3). 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 centre of the receptive field to W3B-RGCs, which could improve their ability to judge the synchrony of local and global motion.