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了解视觉皮层中的神经回路如何计算皮层神经元的响应特性，以及这些特性如何有助于视觉感知。为了研究皮层计算，我们首先需要识别电路本身，并了解它们是如何相对于视觉皮层的功能结构进行组织的。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，因为它们显示出高度专业化的组织。最初认为V2的三条平行加工途径（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）。最近的研究对这一模型进行了修正，提出只有两条通向V2的通路离开V1，一条通向细条纹，另一条通向浅色和粗条纹。随着苍白和粗条纹从V1接收到共同的信息，视觉系统中的并行处理模型正在受到挑战。然而，厚和苍白的条纹隔离他们的输出到具有不同的功能专业化的皮层区域。这一观察结果以及对最近解剖学数据的批判性评价表明，苍白和粗条纹反而可能接收来自V1的隔离输入。我们建议使用逆行示踪剂注射针对功能鉴定（使用光学成像- OI）特定的V2条纹，和定量解剖方法，以测试的假设，超过两个隔离的途径V2离开V1。使用一种新的逆行病毒示踪剂（基因修饰的GFP表达狂犬病病毒）标记树突状和轴突的单一V1输出细胞的乔木，我们进一步建议检查，在单细胞水平上，不同的V2条纹的V1输出途径的专业化程度。特别是，我们将测试的假设，即V1预测不同的V2条纹来自不同的细胞群体。关于V1输出通路如何组织相对于V1和V2的视觉刺激功能的皮层地图的信息是必要的，以了解其计算的作用。V2神经元在不同CO条纹上的反应特性表明，薄条纹参与表面加工，而厚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用于处理对象轮廓的不同方面。为了确定什么以及如何V1有助于V2细胞的响应特性，我们建议检查，在神经元群体和单细胞水平上，V1输出途径不同的V2条纹是如何组织相对于retinotopic地图，和地图的视觉刺激的方向和空间频率在V1和V2。逆行示踪剂和狂犬病-GFP病毒将被共同注射到特定V2条纹内的特定方向或空间频率域中，由OI识别。将定量分析V1特征图上所得标记细胞和终扣的分布。这些研究将提供对早期视觉系统中并行信息处理的深入了解，以及V1到V2的输出路径所执行的计算类型。公共卫生相关性：正常的视力取决于视觉皮层回路的有序发育及其完整功能。我们对处于视觉处理早期阶段的V1和V2皮质区之间的正常回路的研究，也将提供更深入的了解，当这些回路因中风或其他损伤而受损时，中央视觉缺陷的原因和影响。

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.