Effects of Regional Neural Architecture on Signal Processing in the Macaque Retina - PROJECT SUMMARY The retina employs a multitude of parallel neural circuits to encode the many aspects of vision. At all light levels, and in all circuits, cellular noise threatens the accurate encoding of visual stimuli. To combat noise, the retina uses circuit and synaptic mechanisms to amplify signal and filter out noise. Two examples of this are nonlinear convergence, the filtering and subsequent pooling of many neural signals into one neuron, and divergence, the spreading of a single signal into many neurons. Two important neural circuits that emphasize the presence, or lack, of circuit mechanisms, are the rod pathway and foveal midget pathway, respectively. The rod pathway uses high degrees of nonlinear convergence to amplify single photon signals enabling vision in extremely dark environments. The foveal midget pathway encodes hyperfine spatial detail by doing away with circuit mechanisms such as convergence and divergence in exchange for 1:1 connections between neurons. The relative density of neurons in the retina varies across retinal regions influencing the degree of convergence/divergence, and thus the magnitude of noise in neural circuits. While rod pathway sensitivity has been studied in peripheral macaque retina, where convergence is high and cell density is low, the question of how cellular connection augments rod pathway sensitivity across regions has yet to be answered. This is all the more salient due to recent literature which has pointed to regions with lower convergence but higher cell density as having the highest dim light sensitivity. My project proposes to look at single cell metrics of rod pathway sensitivity in these retinal regions. The foveal midget pathway is capable of responding to minute variations in contrasts to encode the fine spatial detail of our foveal vision. It manages to do so in the absence of convergence or divergence to amplify signal. The question remains: “how has signal processing in the foveal midget pathway adapted to a lack of key circuit mechanisms?” My project proposes to determine if regularity in synaptic release is the mechanism by which the foveal midget circuitry encodes information in the absence of prominent circuit mechanisms like convergence and divergence. This project will bridge the gap between our mechanistic understanding of rod pathway sensitivity and the regional sensitivity indicated by psychophysical studies – providing a more complete understanding of how varied cellular connectivity affects our most sensitive retinal pathway. Given the importance of our high-acuity foveal vision and the relative lack of understanding of foveal signal processing, this project will determine key mechanisms enabling foveal vision to operate with hyperfine spatial acuity. The pursuit of this project will enhance our understanding of how the neural code changes as a consequence of varied cellular connectivity.