Anatomical and Functional Interrogation of Parallel Visual Pathways from Eye to Brain

项目摘要/摘要 这项提议的长期目标是表征鼠标视觉中特定电路的连接 其总体结构在从老鼠到灵长类的物种中高度保守的系统。我们的目标是 为了识别从视网膜传递视觉信息的神经回路，通过视网膜的不同区域 背外侧膝状核(DLGN)，至初级视皮层(V1)的特定神经元群 对视觉感知和行为有贡献。这一提议的中心假设是：(1)神经元 在dLGN的外壳和核心中从视网膜接收不同类型的视觉信息，因此， 可将不同类型的视觉信息传递给V1神经元；(2)V1核壳输入的平衡 神经元受到影响，它们的调谐特性。这项提案中概述的实验将测试这些 通过追求三个特定目标的假设：(1)鉴定和鉴定视网膜神经节细胞(RGC) 为dLGN核心的神经元提供输入的类型，以及这些dLGN神经元 V1中的接触；(2)确定V1中遗传识别的神经元是否接受来自独特模式的输入 以及(3)确定来自dLGN核心神经元的输入如何影响 遗传识别的V1神经元群体。这项提议在技术上是创新的；它将使用新颖的 以及狂犬病电路追踪、全细胞记录、光遗传刺激、 化学发生沉默和双光子钙成像，以实现其目标。拟议的研究将 产生重要的发现，这些发现将为信息如何编码、处理和 最终通过老鼠的视觉通路传播。这些发现至关重要，因为 在这些路径中执行的计算生成视觉场景的表示，并最终使 对感知和行为的特性贡献。拟议的研究还将有助于确定 鼠标视觉系统中的视觉处理模仿或不模仿 灵长类视觉系统。了解计算在视觉通路中执行的程度 小鼠和灵长类动物视觉系统的重叠对于决定如何在小鼠身上进行研究至关重要 视觉系统转化为灵长类动物--因此也就是人类--视觉系统。事实上，要想成功 制定恢复视力的策略，克服各种视觉系统疾病，关键是首先 理解视觉系统如何产生我们对周围世界的感觉。这里提出的工作将 毫不含糊地让我们更接近这一目标。

Project Summary/Abstract The long-term goal of this proposal is to characterize the connectivity of specific circuits in the mouse visual system whose gross architecture is highly conserved across species from mouse to primate. The objective is to identify the neural circuits that transmit visual information from the retina, through different regions of the dorsal lateral geniculate nucleus (dLGN), to specific populations of neurons in the primary visual cortex (V1) that contribute to visual perception and behavior. The central hypotheses of this proposal are: (1) that neurons in the shell and core of the dLGN receive different types of visual information from the retina and, therefore, can transmit different types of visual information to V1 neurons; (2) The balance of core and shell input that V1 neurons receive influences their tuning properties. The experiments outlined in this proposal will test these hypotheses by pursuing three specific aims: (1) Identifying and characterizing the retinal ganglion cell (RGC) types that provide input to neurons in the core of the dLGN, as well as the neurons that those dLGN neurons contact in V1; (2) Determining whether genetically-identified neurons in V1 receive input from unique patterns of RGCs; and (3) Determining how input from neurons in the core of the dLGN influence tuning properties in genetically-identified populations of V1 neurons. This proposal is technologically innovative; it will use novel mouse lines as well as a combination of rabies circuit tracing, whole-cell recording, optogenetic stimulation, chemogenetic silencing, and two-photon calcium imaging to accomplish its aims. The proposed research will yield significant findings that will provide considerable insight into how information is encoded, processed, and ultimately transmitted throughout the mouse visual pathway. These findings are of utmost importance as the computations performed in these pathways generate a representation of the visual scene and ultimately make characteristic contributions to perception and behavior. The proposed research will also help determine the extent to which visual processing in the mouse visual system does, or does not, mimic visual processing in the primate visual system. Understanding the extent to which computations performed in the visual pathway overlap in mouse and primate visual systems is critical for determining how research done in in the mouse visual system translates to the primate — and therefore human — visual system. Indeed, to successfully develop strategies to restore sight across a wide range of afflictions of the visual system, it is critical to first understand how the visual system gives rise to our sense of the world around us. The work proposed here will unequivocally move us closer to this goal.