Formation of Cortical Areas and Circuits

描述(申请人提供)：本方案的总体目标是确定小鼠纹外视皮质的区域图，视野在这些区域中如何表示，不同区域是否连接到背侧和腹侧路径，以及它们是否代表功能上的专门处理流。在初步研究中，我们追踪了同一动物V1的三个不同点的输出，揭示了视觉皮质中的十个地形图。多单位记录的感受野映射表明，每个区域都包含一张有序的视野图。对每个地区产出的顺行追踪进一步揭示了一个联系网络，这表明各地区是按等级组织的，并由相互交织的腹流和背流联系在一起。腹流区和背流区的初步单单位记录显示，方向选择神经元在背流区的出现率较高。结果表明，腹侧和背侧通路代表了不同的视觉加工流，这可能对应于灵长类动物的“什么”流和“哪里”流。这是第一次证明老鼠的视觉皮质与灵长类动物有着共同的皮质组织原则，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，已经证实了影响背侧和腹侧流区功能的失认症的遗传易感性。为了研究这些疾病的潜在分子和突触机制，了解小鼠模型中视皮层的结构和功能是必不可少的。鉴于Felleman和Van Essen(1991)区域图对视觉神经科学的影响，这必须首先包括区域的识别、区域层次的表征和加工流的描述。尽管有老鼠和小鼠的区域地图，但它们在物种内部和物种之间存在巨大差异。这些分歧是由于动物汇集在一起，以及使用不充分的解剖地标对部分地图进行了糟糕的登记。我们建议用一种新的方法来解决这些冲突，该方法直接结合解剖学路径追踪(目标1)和生理感受野映射(目标2)来定义区域。以前还没有在啮齿动物身上研究区域间溪流。因此，拟议的背侧和腹侧流连接的追踪研究(目标#3)结合背侧和腹侧流区域方向选择反应的单一单位记录(目标#4)在概念上是新颖的。这项拟议的研究的意义在于补充灵长类皮质的功能研究，并为未来研究人类视觉系统的分子和突触基础提供一个小鼠模型。

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.