Effects of local adaptation on parallel pathway circuit computations in the retina

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PROJECT SUMMARY/ABSTRACT The retina is an adaptable circuit that is capable of rapidly changing its processing mode with changing stimulus conditions. This is an enormous undertaking because the retina has to process an unpredictable and wide-ranging assortment of inputs. An understanding of how local neuron dynamics are coordinated to produce and alter global network computations is needed for understanding how neural circuits of the brain are able to flexibly integrate information from many different areas. Advances on this front will have a broad impact on the ability to design targeted therapies to ameliorate brain disorders. The long-term goal of the proposed work is to understand how local adaptation mechanisms impact the computational function of neural circuits like the retina. Signals from the photoreceptors are processed along parallel pathways in the early part of the retina circuit and later combined. The properties of the visual inputs can modulate the how these inputs are processed via local adaptation mechanisms. This kind of adaptation has consequences for the manner in which visual inputs are encoded and processed in the early part of the visual system. The proposed research during the mentored phase aims to characterize the rod pathway adaptation that leads to a switch in computational processing of inputs and to determine the consequences for the spatiotemporal encoding of visual inputs. I will characterize adaptation through the rod-AII pathway for a range of luminance conditions to build a predictive model and to then determine how this adaptation affects the feature-sensitivity of ON α- ganglion cells under different luminance conditions. The independent phase research will build on the progress made during the mentored phase. There are several distinct ganglion cell types that convey information to the brain about particular visual features - similar to the higher order processing that takes place in the visual cortex. I will conduct studies to determine how ON and OFF α-ganglion cell types use the same circuitry to produce computations that are fundamentally distinct beyond their opposite polarities. The objective of this work is to obtain a better understanding of how mechanisms of local adaptation can reconfigure the computational functions of diverse circuit components. The University of Washington offers the ideal environment for my career development and for pursuing this highly interdisciplinary project. I have two outstanding mentors, an experimentalist and a theorist. I will receive training to become proficient in retina electrophysiology experiments and take courses to hone my quantitative skills. This training will prepare me to launch my own lab with an interdisciplinary focus. The proposed research will establish my expertise in the effects of biophysical mechanisms on sensory circuit computation.