Formation of Cortical Areas and Circuits

描述（由申请人提供）：本提案的总体目标是确定小鼠纹外视皮层的区域图，这些区域如何表示视野，不同区域是否连接到背侧和腹侧通路，以及它们是否代表功能专门化的处理流。初步研究中，我们追踪了同一动物V1的三个不同点的输出，揭示了视觉皮层的十个地形图。通过多单位记录的感受野映射已经表明，每个区域包含一个有序的视野图。顺行追踪每个区域的输出进一步揭示了一个连接网络，这表明这些区域是分层组织的，并通过交织的腹侧流和背侧流连接起来。在腹侧和背侧流领域的初步单单位录音表明，方向选择性神经元的发病率较高的背侧流。结果表明，腹侧和背侧通路代表不同的视觉处理流，这可能对应于灵长类动物的“什么”和“哪里”流。这是第一次证明老鼠的视觉皮层与灵长类动物有几个共同的皮层组织原则，并表明老鼠是人类大脑的一个很好的模型。最近的分子遗传学研究已经确定了数十种影响大脑皮层的基因突变。此外，遗传倾向已被证明为失认症，影响功能的背侧和腹侧流区。为了研究这些疾病的潜在分子和突触机制，有必要了解小鼠模型中视觉皮层的结构和功能。鉴于Felleman和货车埃森（1991）的视觉神经科学领域图的影响，这必须首先包括区域的识别，区域层次的表征和处理流的描述。虽然大鼠和小鼠的区域地图是可用的，但它们在物种内和物种之间存在很大差异。不一致是由于动物之间的合并和使用不充分解剖标志的部分标测图配准不良。我们提出了一种新的方法，直接结合解剖路径跟踪（目标#1）和生理感受野映射（目标#2）来定义区域，以解决这些冲突。以前没有在啮齿动物中研究过间隙流。因此，所提出的背侧流和腹侧流连接的追踪研究（目标#3）结合背侧流和腹侧流区域的方向选择性反应的单个单元记录（目标#4）在概念上是新颖的。这项研究的意义在于补充灵长类动物皮层的功能研究，并为人类视觉系统的分子和突触基础的未来研究提供小鼠模型。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to determine the area map of mouse extrastriate visual cortex, how the visual field is represented in these areas, whether different areas are connected to dorsal and ventral pathways and whether they represent functionally specialized processing streams. Preliminary studies, in which we have traced the outputs from three different points of V1 in the same animal, have revealed ten topographic maps in visual cortex. Receptive field mapping by multiunit recording has shown that each area contains an orderly map of the visual field. Anterograde tracing of outputs from each area have further revealed a network of connections, which suggests that areas are hierarchically organized and are linked by intertwined ventral and dorsal streams. Preliminary single-unit recordings in ventral- and dorsal-stream areas show that the incidence of direction selective neurons is higher in the dorsal stream. The results suggest that ventral and dorsal pathways represent distinct visual processing streams, which may correspond to 'what' and 'where' streams in primates. This is the first demonstration that mouse visual cortex shares several principles of cortical organization with primates and suggests that the mouse is a good model of the human brain. Recent molecular genetic studies have identified dozens of gene mutations that affect cerebral cortex. In addition, genetic predispositions have been demonstrated for agnosias that affect the functioning of dorsal and ventral stream areas. To study the underlying molecular and synaptic mechanisms of these disorders it is essential to understand the structure and function of visual cortex in the mouse model. Given the impact of the Felleman and Van Essen (1991) area diagram for visual neuroscience, this must include first and foremost the identification of areas, the characterization of the areal hierarchy and the description of processing streams. Although area maps are available for rat and mouse, they differ enormously within and between species. The disagreements are due to pooling across animals and poor registration of partial maps using inadequate anatomical landmarks. We propose to resolve these conflicts with a novel approach that directly combines anatomical pathway tracing (Aim #1) and physiological receptive field mapping (Aim #2) to define areas. Interareal streams have previously not been studied in rodents. Thus, the proposed tracing studies of dorsal- and ventral-stream connections (Aim #3) combined with single unit recording of direction selective responses in dorsal and ventral stream areas (Aim #4) are conceptually novel. The significance of the proposed investigation is to complement functional studies in primate cortex and provide a mouse model for future studies of the molecular and synaptic basis of the human visual system.