Parallel pathways in visual cortex: functional connectivity of output pathways fr

描述（由申请人提供）：神经科学的一个主要挑战是理解视觉皮层中的神经回路如何计算皮层神经元的反应特性，以及这些特性如何促进视觉感知。为了研究皮层计算，我们首先需要识别回路本身，并了解它们是如何根据视觉皮层的功能结构组织起来的。从初级视觉皮层（V1）到次级视觉区（V2）的输出通路是研究皮层计算的一个很好的模型，因为它们显示了一个高度专业化的组织。最初认为，有三条平行的V2加工途径（分别用于处理颜色、形状和立体视觉）离开V1，并分离成不同的V2亚区（厚、薄和苍白的细胞色素氧化酶- co -条纹）。最近的研究修改了这一模型，并提出只有两条途径到达V2离开V1，一条是薄条纹，另一条是浅条纹和厚条纹。当苍白和粗大的条纹从V1接收到共同的信息时，视觉系统中的并行处理模型正在受到挑战。然而，粗条纹和淡条纹将它们的输出分离到具有不同功能专门化的皮层区域。这一观察结果以及对最近解剖学数据的批判性评估表明，苍白和厚实的条纹可能从V1接收分离的输入。我们建议使用逆行示踪剂注射靶向功能识别（使用光学成像- OI）特定的V2条纹，并使用定量解剖学方法，来验证不止两条分离的路径从V1离开V2的假设。利用一种新型逆行病毒示踪剂（一种基因修饰的表达GFP的狂犬病毒）标记单个V1输出细胞的树突和轴突，我们进一步提出在单细胞水平上检测V1输出途径对不同V2条纹的专门化程度。特别是，我们将检验V1投射到不同V2条纹的假设，这些条纹来自不同的细胞群。关于V1和V2的视觉刺激特征的皮层图如何组织V1输出通路的信息对于理解它们的计算作用是必要的。不同CO条纹的V2神经元响应特性表明，细条纹参与表面加工，粗条纹和淡条纹参与轮廓加工。粗条纹和淡条纹可以进一步专门处理物体轮廓的不同方面。为了确定V1对V2细胞的反应特性有何贡献以及如何贡献，我们建议在神经元群体和单细胞水平上研究V1输出到不同V2条纹的通路是如何根据视网膜定位图、V1和V2的视觉刺激方向和空间频率图组织起来的。逆行示踪剂和狂犬病-绿色荧光蛋白病毒将被共同注射到由OI识别的特定V2条纹内的特定方向或空间频率域。得到的标记细胞和钮扣在V1特征图上的分布将被定量分析。这些研究将深入了解早期视觉系统中的并行信息处理，以及V1输出到V2的各种计算。公共卫生相关性：正常视力依赖于视觉皮层回路的有序发育及其完整的功能。我们对处于视觉处理早期阶段的皮层区域V1和V2之间的正常电路的研究，也将为当这些电路因中风或其他损伤而受损时中枢视觉缺陷的原因和影响提供更深入的了解。

Description (provided by applicant): A major challenge in neuroscience is to understand how neural circuits in the visual cortex compute the response properties of cortical neurons, and how these contribute to visual perception. To study cortical computations, we first need to identify the circuits themselves, and to understand how they are organized with respect to the functional architecture of the visual cortex. The output pathways from the primary visual cortex (V1) to the secondary visual area (V2) are a good model to study cortical computations, because they show a highly specialized organization. It was first thought that three parallel processing pathways to V2 (for the processing of color, form and stereopsis, respectively) leave V1, and segregate into distinct V2 subregions (thick, thin and pale cytochrome-oxidase -CO- stripes). Recent studies have revised this model and proposed that only two pathways to V2 leave V1, one to the thin stripes, the other to both pale and thick stripes. With pale and thick stripes receiving a common message from V1, models of parallel processing in the visual system are being challenged. However, thick and pale stripes segregate their outputs to cortical areas having different functional specialization. This observation, and a critical evaluation of the recent anatomical data, suggests that the pale and thick stripes instead may receive segregated inputs from V1. We propose to use retrograde tracer injections targeted to functionally identified (using optical imaging - OI) specific V2 stripes, and quantitative anatomical methods, to test the hypothesis that more than just two segregated pathways to V2 leave from V1. Using a novel retrograde viral tracer (a genetically modified GFP- expressing rabies virus) to label dendritic and axonal arbors of single V1 output cells, we further propose to examine, at the single cell level, the degree of specialization of the V1 output pathways to different V2 stripes. In particular, we will test the hypothesis that V1 projections to different V2 stripes arise from distinct cell populations. Information on how V1 output pathways are organized with respect to the cortical maps of visual stimulus features in V1 and V2 is necessary to understand their computational role. The response properties of V2 neurons in different CO stripes suggest that thin strips are involved in surface processing, and thick and pale stripes in contour processing. Thick and pale stripes may be further specialized in processing different aspects of object contours. To determine what and how V1 contributes to the response properties of V2 cells, we propose to examine, at the neuronal population and single cell level, how the V1 output pathways to different V2 stripes are organized with respect to the retinotopic maps, and maps of visual stimulus orientation and spatial frequency in V1 and V2. Retrograde tracers and the rabies-GFP virus will be co-injected into specific orientation or spatial frequency domains within specific V2 stripes, identified by OI. The distribution of resulting labeled cells and boutons on the V1 feature maps will be quantitatively analyzed. These studies will provide insight into parallel information processing in the early visual system, and into the kinds of computations that are performed by the V1 output pathways to V2. PUBLIC HEALTH RELEVANCE: Normal vision depends on the orderly development of circuits in the visual cortex and on their intact function. Our studies of the normal circuitry between cortical areas V1 and V2, which are at the early stages of visual processing, will also provide greater insight into the causes and effects of central vision defects when these circuits are damaged by stroke or other insult.