Mammalian ganglion cells (GCs) comprise more than a dozen distinct types, differing in structure, light responses, projections to the brain, and probable function. The long-term goal of this research is to understand the functional significance of this diversity and its anatomical and physiological substrates. The experiments proposed here focus on ON-OFF GCs, a group of cells excited by both light and dark stimuli in their receptive field centers. ON-OFF GCs are ubiquitous among vertebrates, including primates, and are more common in mammals than generally appreciated. Their transient light responses, motion sensitivity and strong preferences for spatially-restricted stimuli point to possible roles in detection and localization of moving objects. Though extensively studied in cold-blooded vertebrates, ON-OFF GCs have been largely neglected in mammals because of the relative prominence and ease of study of other types (e.g., X and Y; M and P). The proposed research will exploit new methods that overcome technical barriers to the study of ON-OFF GCs. Pilot structure-function data in cat suggest marked heterogeneity among these cells. They belong to at least five distinct morphological types, differing in dendritic form and central projections. One goal of this study is to provide comprehensive descriptions of these types and a sound empirical basis for distinguishing them. The structural heterogeneity is presumably related to the functional diversity among this cell population (e.g., in direction selectivity and the relative strength of ON and OFF channel input). Thus, a second goal is to compare and contrast the visual response properties of ON-OFF GCs belonging to each of these morphological types. These cells have receptive fields with powerful suppressive surrounds, which strongly constrain optimal stimulus size. The synaptic basis of this property has been well studied in amphibians, but it is unknown whether the emerging circuit model applies to the mammalian retina. Proposed studies will address this question. Whole-cell patch-clamp recordings of light-responsive ON-OFF cells will be made in an intact superfused retina-choroid preparation that preserves the spatial structure of receptive fields. Light stimulation of the receptive field will be combined with pharmacological perturbation of synaptic networks and manipulation of transmembrane voltage. Cells will be stained by intracellular injection, in some cases after retrograde labeling from specific visual nuclei of the brain. The study will expand our understanding of how diverse GC types implement the range of transformations of the retinal image carried out by the mammalian retina.
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