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

描述(申请人提供)：神经科学中的一个主要挑战是了解视觉皮质中的神经回路如何计算皮质神经元的反应特性，以及这些特性如何影响视觉感知。为了研究大脑皮层计算，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质的功能架构组织起来的。从初级视觉皮质(V1)到次级视觉区域(V2)的输出通路是研究皮质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。人们最初认为，V2的三条平行加工路径(分别用于颜色、形状和立体视觉的加工)离开V1，并分离成不同的V2亚区(粗、薄和淡细胞色素-氧化酶-CO条纹)。最近的研究修正了这一模型，提出V2只有两条途径离开V1，一条通往细条纹，另一条通往浅条纹和粗条纹。随着苍白和粗大的条纹从V1接收到共同的信息，视觉系统中的并行处理模式受到了挑战。然而，粗条和浅条将它们的输出分隔到具有不同功能专门化的皮质区域。这一观察和对最近解剖学数据的关键评估表明，苍白和粗大的条纹可能接受来自V1的分离输入。我们建议使用逆行示踪剂注射来从功能上识别(使用光学成像-OI)特定的V2条纹，并使用定量解剖学方法来检验这一假设，即不止两条分离的路径从V1离开V2。使用一种新的逆行病毒示踪剂(一种表达GFP的转基因狂犬病病毒)来标记单个V1输出细胞的树突状和轴突树枝，我们进一步建议在单细胞水平上检查V1输出通路到不同V2条带的特化程度。特别是，我们将测试V1到不同V2条纹的投影来自不同的细胞群体的假设。关于V1输出通路是如何相对于V1和V2中的视觉刺激特征的皮层映射进行组织的信息对于理解它们的计算作用是必要的。V2神经元在不同CO纹中的反应特性表明，细纹状体参与表面加工，粗条纹和浅纹状体参与轮廓加工。在处理物体轮廓的不同方面时，粗条纹和淡条纹可以进一步专门化。为了确定V1对V2细胞的反应特性有什么作用以及如何作用，我们建议在神经元群体和单细胞水平上研究V1到不同V2条纹的输出路径是如何根据视网膜定位图以及V1和V2中的视觉刺激方向和空间频率图来组织的。逆行示踪剂和狂犬病-GFP病毒将被共同注射到特定V2条带内的特定方向或空间频率域，由OI识别。将定量分析V1特征地图上所产生的标记单元和连续单元的分布。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到V2的输出路径执行的计算类型。与公众健康相关：正常的视力取决于视皮层回路的有序发展及其完整的功能。我们对处于视觉处理早期阶段的皮质区域V1和V2之间的正常回路的研究，也将提供更多关于中央视觉缺陷的原因和影响的见解，当这些回路因中风或其他侮辱而受损时。

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.