Layer 6 corticocortical neurons are a major route for intra and interhemispheric feedback

Abstract

The mouse neocortex contains at least ninety distinctly defined yet interconnected areas that are symmetrically located across the two hemispheres. Determining the logic of this long range circuitry is necessary for understanding how inter-areal integration enables high level brain function involving multiple sensory, motor and cognitive processes. To address this we have performed a systematic anatomical analysis of the areal and laminar organization of the ipsilateral and contralateral cortical projection onto the primary visual (VISp), primary somatosensory barrel field (SSp-bfd) and primary motor (MOp) cortices. The resultant input maps reveal that although the ipsilateral hemisphere is the primary source of cortical input, there is substantial bilateral symmetry regarding the relative contribution and areal identity of contralateral input. Laminar analysis of these input areas show that excitatory Layer 6 corticocortical cells (L6 CCs) are a major projection pathway from both within and across the two hemispheres. Based on cortical hierarchy analysis that compares the relative contribution of inputs from supra-(feedforward) and infra-granular (feedback) layers, we find that contra-hemispheric projections reflect a dominant feedback organization compared to their ipsi-cortical counterpart. The magnitude of the interhemispheric difference in hierarchy was largest for sensory and motor projection areas compared to frontal, medial or lateral brain areas and can be explained by a proportional increase in input from L6 neurons. L6 CCs therefore not only mediate long-range cortical communication but also reflect its inherent feedback organization.