Synaptic Transmission in The Rod Pathway of the Mammalian Retina

Project Summary: The broad goal of this proposal is to understand how neurons are organized into circuits and how neural circuit function arises from the intrinsic properties of component cells and synapses. The mouse retina serves as the model system because of its well-understood organization and function and because mouse models offer powerful genetics-based tools. Our goal is to understand how synaptic inhibition by amacrine cells (ACs) generates the functional diversity of retinal output channels: i.e., the unique responses of individual ganglion cell (GC; the retinal output neuron) types to a visual stimulus. This objective is related to broader studies that have highlighted the morphological, genetic, and functional diversity of inhibitory neurons in the retina and elsewhere in the central nervous system. Our focus will be on synaptic inhibition of the best-characterized GCs in the mouse retina: the “alpha” GCs, which include the ON α GC, the OFF α GC, and the OFF δ GC. Primarily, we will examine circuits presynaptic to the OFF δ GC to determine how different genetically-identified AC types act to shape the OFF δ GC receptive field. Very broadly, a visual stimulus that depolarizes an inhibitory AC strongly will suppress a postsynaptic GC: thus, AC activity may serve to suppress GC responses to particular regions of stimulus space (e.g. high spatial frequencies), thereby enhancing the response to other regions of stimulus space (e.g. low spatial frequencies). To describe the component of retinal computation encoded by the output of a single AC, the response of that AC to visual stimuli must be understood and the dynamics of transmission from its synapses assayed. Knowing both the connectivity of the AC, the features of the visual scene that depolarize it, and the behavior of its output synapses will provide insight into its circuit function. We therefore will combine ultrastructural and electrophysiological assays to understand how different AC types act to shape GC outputs. Relevance to Public Health: Understanding how visual stimulus coding is implemented by retinal synapses informs the design of retinal prosthetics and the study of animal models of human retinal diseases. The proposed work clarifies how visual signal processing is modulated at three stages in the retinal network and addresses two goals of the Retinal Diseases Program in the National Plan for Eye and Vision Research: one, it builds on knowledge gained from retinal neuroscience to understand how retinal networks process visual images, and two, it works toward identifying the post-photoreceptor neural components of adaptation.