Cell-type-specific parallel pathways in the canonical cortical microcircuit

Zhang, C.; Schneider-Mizell, C. M.; Danskin, B. P.; Swanstrom, R.; Neace, E.; Joyce, E.; Pedigo, B. D.; Collman, F. C.; Macarico da Costa, N.

doi:10.64898/2026.04.23.720412

bioRxiv · 10.64898/2026.04.23.720412

Cell-type-specific parallel pathways in the canonical cortical microcircuit

Zhang, C.·Schneider-Mizell, C. M.·Danskin, B. P.·Swanstrom, R.·Neace, E.·Joyce, E.·Pedigo, B. D.·Collman, F. C.·Macarico da Costa, N.

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Abstract

Information processing in the cortex depends on the integration of bottom-up and top-down signals through recurrent microcircuits spanning layers. Although the canonical microcircuit provides a framework for this integration, how these interactions are implemented at synapse resolution remains unclear. Here, we use large-volume electron microscopy reconstructions of mouse primary visual cortex to map the intralaminar and interlaminar connectivity of intratelencephalic (IT) neurons in layers 2/3 and 5. We find that layer 2/3 IT neurons formed a depth-dependent gradient of recurrent connectivity, with superficial (L2) and deeper (L3) neurons potentially forming two channels associated with top-down and bottom-up processing, respectively. These channels are preserved across layers via cell-type-specific pathways involving distinct L5 IT types, rather than collapsing into a single integrative pool. Moreover, each channel is regulated by a largely separate cohort of inhibitory interneurons, stabilizing recurrent excitation while limiting crosstalk. Together, these results reveal parallel, cell-type-specific processing streams embedded within the canonical circuit.

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Zhang, C., Schneider-Mizell, C. M., Danskin, B. P., Swanstrom, R., Neace, E., Joyce, E., Pedigo, B. D., Collman, F. C., Macarico da Costa, N.. 2026-04-24. Cell-type-specific parallel pathways in the canonical cortical microcircuit. https://doi.org/10.64898/2026.04.23.720412

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