The assembly and function of motion selective circuits in the retina

Complex patterns of synapses connect neurons together and create circuits critical for our mental abilities. We are interested in how these wiring patterns arise and how particular wiring patterns endow circuits with functional properties. To learn more, we study the retina, where ~30 types of retinal ganglion cells (RGCs) analyze the visual scene, each specialized to detect a unique feature such as motion, colour, edges, and so on. The general consensus is that RGCs are endowed with their feature preferences via the synaptic input they receive from a specific subset of interneurons (~100 types). How do specific interneuron-RGC connections arise? What are the factors that direct these specific connections? What is the significance of these early wiring choices for feature detection? Addressing these issues is the core of my research program. Using a combination of molecular-genetic, physiological, optogenetic and systems approaches we mapped the interneuron connectivity formed on two motion selective RGCs, identified the interneurons critical for their feature selectivity, and discovered that wiring genes are critical for their assembly. These genes, called recognition molecules, are members of the cadherin (Cdh) and immunoglobulin (Ig) superfamilies and are critical for circuit function; genetic deletion of Ig and Cdh members results in specific wiring deficits which in turn ablate specific aspects of RGC motion selectivity. Our results suggest a potential model for circuit assembly in which Cdhs direct neurons to grow processes into particular neuropil layers to come in proximity with potential synaptic targets, whereas Igs direct them to synapse with only a few of these proximate alternatives. Our near-term goals are to seek evidence in support of this model in retina. Further out, we want to leverage our knowledge to examine the role of the widespread, combinatorial expression pattern of Cdhs and Igs found at higher centers in the brain.