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

视网膜是一种适应性很强的电路，它能够通过 不断变化的刺激条件。这是一项巨大的任务，因为视网膜必须处理 不可预测的、范围广泛的投入。对局部神经元动力学的理解 协调以生成和更改全球网络计算，以了解 大脑的神经回路能够灵活地整合来自许多不同区域的信息。 这方面的进展将对设计靶向治疗的能力产生广泛影响 改善脑部疾病。拟议工作的长期目标是了解当地 适应机制会影响像视网膜这样的神经回路的计算功能。信号 来自光感受器的光信号在视网膜的早期沿着平行的路径进行处理 电路和后来的组合。视觉输入的属性可以调整这些输入的方式 是通过当地适应机制处理的。这种适应会对 在视觉系统的早期部分对视觉输入进行编码和处理的方式。这个 在指导阶段提出的研究旨在表征杆状通路的适应 导致输入计算处理的切换，并确定 视觉输入的时空编码。我将通过棒-AII来描述适应 一系列亮度条件的路径以建立预测模型，然后确定如何 这种适应影响了不同亮度下Onα神经节细胞的特征敏感性 条件。独立阶段的研究将建立在指导期间取得的进展的基础上 相位。有几种不同的神经节细胞类型向大脑传递关于 特定的视觉特征-类似于在视觉中发生的更高级别的处理 大脑皮层。我将进行研究，以确定α神经节细胞类型如何使用相同的 一种电路，用于产生完全不同于相反极性的计算。 这项工作的目标是更好地了解地方政府 自适应可以重新配置不同电路组件的计算功能。这个 华盛顿大学为我的职业发展和追求提供了理想的环境 这个高度跨学科的项目。我有两位杰出的导师，一位是实验者，一位是 理论家。我将接受培训，精通视网膜电生理实验和 参加一些课程来磨练我的量化技能。这次培训将为我建立自己的实验室做好准备 具有跨学科的焦点。拟议的研究将建立我在影响方面的专业知识 关于感觉回路计算的生物物理机制。

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.