Formation of Cortical Areas and Circuits

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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.