Cone Integration in the visual cortex

摘要 核心神经科学研究的一个问题是理解感觉神经元是如何连接到 帮助生物体导航的特征。视觉从光感受器马赛克开始，随后 通过精致的视网膜电路立即检测对比度和颜色的基本变化， 一幅图画。在视网膜之外，视皮层的连续阶段逐渐整合平行的 用于创建日益复杂的调谐的信息。视觉神经科学特别适用于 理解大脑皮层执行的计算，部分原因是早期的并行通路始于 可以用标准的视觉显示器以高度可控的方式刺激视网膜。然而，这一领域仍然 缺乏受实验数据约束的皮质功能的详细机制模型，这是必要的 最终将视觉皮质的研究与基于皮质的病理学联系起来。出于这个原因，老鼠的 视觉系统是理解大脑皮层回路的重要模型；老鼠体内的遗传工具允许 研究人员具有无与伦比的灵活性，可以操纵和标记已知的 对皮质功能的独立贡献。除了遗传工具，有色刺激的使用与 对于理解大脑皮层计算的一般策略，鼠标可能特别有用。这项研究使用了 一种视觉刺激和基因敲除小鼠的组合，以定位视网膜的亚群，总体目标是 了解视网膜群体的整合如何有助于体内的多个阶段的处理 视觉皮质。该提议的一个早期目标是产生第一个时空特征 初级视觉皮质(V1)的调谐，作为来自视网膜的视锥输入分布的函数。这 为了利用未来对鼠标视觉中的并行处理流的研究，有必要对特征进行表征 大脑皮层，就像我们的。它还将测试颜色独立于空间和空间编码的假设 视觉场景的动态模式。在下一个目标中，我们将测量大脑皮质连接的基本原理 通过测试V1颜色调谐是通过系统地汇集其前馈输入来形成的假设。这个 另一种假设是，大脑皮层通过“随机”回路建立调谐的层次结构。这些测量结果 可能是由于小鼠感光细胞嵌合体的粗略各向异性。在最终目标中，我们将 研究不同的视觉皮质区域如何通过平行通道进行交流。首先，我们将确定是否 高级视觉区域专用于处理特定的颜色、空间和时间带。这将是遵循的 通过测量中间神经元如何对通路的皮质-皮质整合做出贡献，使用空间 结构光遗传学。该提案的实验设计依赖于基因工具、成像、 电生理学、光遗传学和小鼠视觉系统中颜色调谐的功能结构。

Abstract A problem at the core neuroscience research is to understand how sensory neurons are wired to detect features that aid in the organism's navigation. Vision begins with the photoreceptor mosaic, followed immediately by exquisite retinal circuitry that detects basic changes in contrast and color, at every location of an image. Beyond the retina, successive stages of visual cortex gradually integrate parallel streams of information to create tuning of increasing complexity. Visual neuroscience has been especially useful for understanding the computations performed by the cortex, partly because the early parallel pathways initiated in the retina can be stimulated in a highly controlled manner with standard visual displays. However, the field still lacks detailed mechanistic models of cortical function that are constrained by experimental data, a necessary hurdle to ultimately bridge studies of visual cortex to cortical-based pathologies. For this reason, the mouse's visual system is an important model for understanding cortical circuits; genetic tools in the mouse allow researchers unparalleled flexibility to manipulate and label specific cell-types that are known to make independent contributions to cortical function. In addition to genetic tools, the use of colored stimuli with the mouse may be especially fruitful for understanding general strategies of cortical computation. This study uses a combination of visual stimuli and knock-out mice to target subpopulations of the retina, with the overall goal of understanding how the integration of retinal populations contributes to multiple stages of processing within the visual cortex. An early goal of the proposal is to generate the first characterization of the spatio-temporal tuning in primary visual cortex (V1), as a function of the distribution of cone inputs from the retina. This characterization is necessary to leverage future studies of parallel processing streams in the mouse visual cortex, such as ours. It will also test the hypothesis that color is encoded independently of the spatial and dynamic patterns of a visual scene. In the next aim, we will measure fundamental principles of cortical wiring by testing the hypothesis that V1 color tuning is shaped by systematic pooling of its feedforward inputs. The alternative hypothesis is that the cortex builds hierarchies of tuning by “random” circuits. These measurements are made possible by coarse anisotropy in the photoreceptor mosaic of mice. In the final aim, we will investigate how different visual cortical areas communicate via parallel channels. To begin, we will determine if higher visual areas are dedicated to processing specific bands of color, space, and time. This will be followed by measurements of how interneurons contribute to the cortico-cortical integration of pathways, using spatially structured optogenetics. The experimental design of the proposal relies on genetic tools, imaging, electrophysiology, optogenetics, and the functional architecture of color tuning in the mouse's visual system.