Distinct neurogenic pathways shape the diversification and mosaic organization of cortical output channels.

The cerebral cortex broadcasts its output to subcortical regions through the projections of diverse extratelencephalic (ET) neurons derived from either direct (dNG-ETd) or indirect (iNG-ETi) neurogenesis, but the differential contributions of these neurogenic pathways to cortical output organization remain unknown. Establishing a lineage-based viral targeting strategy in mice, we uncover that ETi massively amplifies and diversifies ETd projections across the cortex. Whereas ETd primarily targets the forebrain and midbrain, ETi dominates the hindbrain (e.g., brainstem/spinal action centers and lemniscal sensory stations), hypothalamic, and neuromodulatory regions with cortical area-specific projections. Numerous corticofugal subpopulations derive solely from iNG-ETi. Area-specific spinal projections of ETi, but not of ETd, emerge from the postnatal pruning of an initial cortex-wide population. In the motor cortex, ETd or ETi activation induced distinct movements: either head-trunk or, additionally, coordinated orofacial-forelimb movements, respectively. Thus, two foundational neurogenic pathways with distinct evolutionary histories differentially shape the area-specific diversification of cortical output channels.

Duke Scholars

Author Josh Huang Neurobiology

Author Shreyas Mysore Suryanarayana