In primates, proximal cortical areas are interconnected via within-cortex ″intrinsic″ pathway, whereas distant areas are connected via ″extrinsic″ white matter pathway. It is not well known how cortical areas are interconnected in small-brained mammals like rodents. In this study, we systematically analyzed the data of Allen Mouse Brain Connectivity Atlas to answer this question and found that the ipsilateral cortical connections in mice are almost exclusively contained within the grey matter with the exception of the retrosplenial area. We analyzed the layer-specific distribution of axonal projections within the grey matter using Cortical Box method and obtained the following results. First, widespread axonal projections were observed in both upper and lower layers in the vicinity of injections, whereas highly specific ″point-to-point″ projections were observed toward remote areas. Second, such long-range projections were predominantly aligned in the anteromedial-posterolateral direction. Third, in majority of these projections, the connecting axons traveled through layer 6. Finally, the projections from the primary and higher order areas to distant targets preferentially terminated in the middle and superficial layers, respectively, suggesting hierarchical connections similar to those of primates. Overall, our study suggests the conserved nature of neocortical organization across species despite conspicuous differences in wiring strategy.

Analysis of ipsilateral corticocortical connectivity in the mouse brain