PROCESSING STREAMS IN MOUSE VISUAL CORTEX

描述（由申请人提供）：视觉系统用于物体识别和视觉引导动作。这些不同的功能是通过从视觉场景中提取空间对比、运动和颜色线索，并将它们发送到中脑和丘脑的专门回路而产生的。在皮层中，来自外侧膝状核的平行输入通道汇合，通过特定的连接混合在一起，产生新的响应特性，这些特性被分类为不同的模块，将输出发送到背侧和腹侧胃外皮层中相互连接的区域的分离流。这些知识大多来自对灵长类动物的开创性研究。然而，目前，如何在灵长类动物身上通过实验将特定分子、神经元和突触回路与特定行为联系起来仍是一个挑战。这些进展似乎对寻找视觉空间障碍和失认症的治疗方法至关重要。许多操纵特定电路的实验工具可用于在鼠标中取得进展。这些新的机会加强了开发鼠标作为研究对象识别和视觉引导行为的网络模型的需要。目前的建议源于迅速传播的认识，即小鼠视觉皮层与灵长类动物的柱状、模块化、区域和分层处理流组织具有基本相似性。这一应用挑战了老鼠初级视觉皮层在水平连接的菊花结构中缺乏功能不同模块的柱和系统图的观点。我们首先发现老鼠的视觉皮层包含近12个不同的区域，这些区域最近被证明是功能专门化的，从而得出了这个观点。我们的研究结果表明，这些不同的皮质特性来自平行的基因皮质通道，专门用于处理空间细节和快速变化的刺激。此外，我们发现在皮层内，这些输入分布在相互连接的区域的背侧和腹侧流中。最近，我们发现小鼠初级视觉皮层包含系统排列的2型毒蕈碱乙酰胆碱受体表达模块，这些模块组织遗传皮质输入，V1内的局部水平连接以及来自高级视觉区域的反馈通路。我们的初步结果表明，这些模块在功能上是专门的，并且不同地连接到背侧和腹侧流。因此，我们假设模块在混合、分类和将不同的信息发送到用于物体识别的颞回路和用于视觉引导动作的后顶叶网络中发挥作用。为了验证这一一般假设，我们建议通过以下方法来确定：1)V1模块输入和输出的解剖追踪和权重分析，2)通道视紫红质辅助的电路映射，解剖连接是否代表特定强度的突触连接，以及3)单个单元记录模块是否具有不同的感受野特性。

DESCRIPTION (provided by applicant): The visual system is used for object recognition and visually guided actions. These diverse functions are generated by extracting spatial contrast, motion and chromatic cues from the visual scene and sending them to specialized circuits in the midbrain and thalamus. In the cortex the parallel input channels from the lateral geniculate nucleus converge, intermix through specific connections that create new response properties, which are sorted into distinct modules that send outputs into segregated streams of interconnected areas in dorsal and ventral extrastriate cortex. Most of this knowledge derives from groundbreaking studies in primates. At present, however, it is challenging to see how it will be experimentally possible in primates to link specific molecules, neurons and synaptic circuits to particular behaviors. Such advances appear to be critical for finding treatments for visuospatial disorders and agnosias. Many experimental tools for manipulating specific circuits are available to make progress in the mouse. These new opportunities have intensified the need to develop the mouse as model for research of networks underlying object recognition and visually guided actions. The present proposal originated from the rapidly spreading recognition that the mouse visual cortex shares basic similarities with the columnar, modular, areal and hierarchical organization of processing streams in primates. The application challenges the view that mouse primary visual cortex lacks columns and systematic maps of functionally distinct modules embodied in the daisy architecture of horizontal connections. We have arrived at this perspective by first finding that mouse visual cortex contains almost a dozen distinct areas which were recently shown to be functionally specialized. Our findings suggest that these diverse cortical properties emerge from parallel geniculocortical channels, specialized for the processing of spatial detail and rapidly changing stimuli. Further, we have found that within the cortex these inputs are distributed into dorsal and ventral streams of interconnected areas. Most recently we have discovered that mouse primary visual cortex contains a systematic array of type 2 muscarinic acetylcholine receptor expressing modules, which organize geniculocortical inputs, local horizontal connections within V1 and feedback pathways from higher visual areas. Our preliminary results demonstrate that these modules are functionally specialized and are differentially connected to dorsal and ventral streams. Thus, we hypothesize that modules play a role in mixing, sorting and sending distinct information into temporal circuits for object recognition and posterior parietal networks for visually guided actions. To test this general hypothesis we propose to determine by: 1) anatomical tracing and weight analysis of the inputs and outputs of V1 modules, 2) channelrhodopsin-assisted circuit mapping whether anatomical connections represent synaptic connections of a specific strength, and 3) single unit recordings whether modules have distinct receptive field properties.