RT Journal Article SR Electronic T1 Descending neocortical output critical for skilled forelimb movements is distributed across projection cell classes JF bioRxiv FD Cold Spring Harbor Laboratory SP 772517 DO 10.1101/772517 A1 Junchol Park A1 James W. Phillips A1 Kathleen A. Martin A1 Adam W. Hantman A1 Joshua T. Dudman YR 2021 UL http://biorxiv.org/content/early/2021/02/22/772517.abstract AB Motor cortex is a key node in the forebrain circuits that enable flexible control of limb movements. The influence of motor cortex on movement execution is primarily carried by either pyramidal tract (PT) neurons, which project directly to the midbrain, brainstem and spinal cord, or intratelencephalic (IT) neurons, which project within the forebrain. The logic of the interplay between these cell types and their relative contribution to the control of forelimb movements remains unclear. Here we combine large-scale neural recordings across all layers of motor cortex with cell-type specific perturbations in a cortex-dependent mouse behavior: kinematically-variable manipulation of a joystick. Our data demonstrate that descending neocortical motor commands are distributed across projection cell classes with partially dissociable functions. Neural recordings revealed IT neuron activity carries a larger fraction of information about gross movement kinematics than is apparent in PT neurons. Optogenetic silencing of Layer 5 PT neurons during movement execution produced small reductions in amplitude and changes in movement trajectory. In contrast, optogenetic silencing of Layer 5 IT projection neurons produced dramatic reductions in movement amplitude. Dorsal striatum is the unique extracortical integration point for IT and PT output pathways and its activity was more dependent upon IT input than PT input during movement execution; consistent with a role of striatum in regulating movement vigor. Thus, these data suggest that the corticostriatal output pathway of IT neurons may be primarily responsible for determining the amplitude and PT output projections are more critical for determining the trajectory and/or coordination of skilled forelimb movements.Competing Interest StatementThe authors have declared no competing interest.