Layer 6 corticocortical cells dominate the anatomical organization of intra and interhemispheric feedback

Cortico-cortical projection neurons couple functionally distinct areas within and between the cortical hemi-spheres via feedback and feedforward pathways that originate from different cortical laminae. Determining the logic of this long range circuitry is necessary for understanding how inter-areal cortical 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 major source of cortical input, there is substantial bilateral symmetry regarding the relative contribution and areal identity of cortical input. Laminar analysis of these input areas show that intra and interhemispheric connectivity is mediated predominantly by excitatory Layer 6 corticocortical cells (L6 CCs). 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, independent of the target injection area. The magnitude of the interhemispheric difference in hierarchy was largest for sensory and motor areas compared to frontal, medial or lateral brain areas and can be explained by a proportional increase in input from L6 projection neurons. L6 CCs therefore not only dominate corticocortical communication but also reflect its inherent feedback organization. ### Competing Interest Statement The authors have declared no competing interest.