Most conscious vision in humans and other primates begins with the fovea, a specialization of the central retina that encodes the image in exceptional detail. The cone photoreceptors of the fovea are tailored for high spatial acuity. They have a tiny cross-section and dense packing, allowing them to form an extremely fine pixel array. Foveal cones also extend long axons that allow downstream cells to be displaced laterally from the light path, providing direct access to the visual image. Each of the principal output neurons of the fovea?the midget retinal ganglion cells (RGCs)?is also driven by a single cone, preserving spatial resolution. By contrast, cones of the peripheral retina are broad, widely spaced, and positioned behind layers of cell bodies and processes; additionally, more than a dozen peripheral cones converge upon single midget RGCs, further reducing spatial resolution. These anatomical specializations of the fovea have been recognized for decades. The overarching hypothesis of this proposal is that foveal cones also possess functional specializations for high-acuity vision. Indeed, a recent publication has indicated that phototransduction is more prolonged in foveal than peripheral cones. The consequences of this distinction are not yet clear. Much depends on how the light responses of foveal cones are shaped downstream of phototransduction, by voltage-gated ion channels (VGICs). Experiments proposed in Aim 1 test the hypothesis that VGICs complement the distinct kinetics of foveal phototransduction. The ability to encode fine spatial detail also depends on the signal/noise ratio. Achieving high signal/noise would appear especially important for foveal cones, which have little opportunity to pool their signals to improve the response fidelity of foveal midget RGCs.
In Aim 2, we test the hypothesis that the signal/noise of foveal cones is increased at multiple stages, including the currents produced by phototransduction and VGICs as well as their effect on the membrane voltage at the soma and synaptic terminal. For both aims, our principal approach is to apply patch-clamp electrophysiology to foveal and peripheral cones that are embedded within retinal circuitry or have been acutely dispersed into single cells. These experiments are complemented by computational modeling. We maintain an experimental platform that supplies us with foveal and peripheral tissue for quantitative analysis. The work proposed here constitutes early steps toward a full understanding of the fovea at the level of cellular neurophysiology.
A leading cause of blindness is macular degeneration. The center of the macula is a structure called the fovea; there, specialized cone photoreceptors initiate most conscious sight and support the high level of spatial resolution that is necessary for tasks like reading and recognizing faces. We seek to investigate the normal function of these cells in order to understand the origin of sharp visual acuity, establish a baseline for diagnosing retinal health, and provide a benchmark for evaluating clinical treatments.
