Neural activity profiles reveal overlapping, intermingled subpopulations spanning area borders in mouse sensorimotor...

Cortical control of movement is a distributed computation spanning multiple densely interconnected regions. Although we have rich anatomical atlases and a coarse understanding of how function maps to areas and subregions, we lack a detailed account of how behaviorally relevant activity is organized across the cortical sheet. Here, we trained head-fixed mice to perform a 15-target reach-to-grasp task while we performed cellular-resolution, two-photon calcium imaging across five regions of sensorimotor cortex (>39,000 layer 2/3 neurons). We characterized each neuron's trial-averaged peri-event activity with interpretable metrics and mapped these response properties across areas, revealing large-scale spatial structure. Neuronal response profiles often shifted abruptly at anatomical borders: motor areas showed sharper tuning and more linear relationships with target location, whereas somatosensory areas displayed more heterogeneous response patterns. Neural response properties also differed according to somatotopic representation. Nonlinear dimensionality reduction of the neural feature matrix revealed that areas varied in their average response profiles, but that areas did not have well-separated feature distributions; instead, each area contained subpopulations. Neurons in each subpopulation had characteristic response profiles and were distributed across multiple cortical areas. The spatial distributions of the subpopulations overlapped, with neurons from different subpopulations salt-and-pepper intermingled in the overlap zones. Together, these results describe novel activity structure across sensorimotor cortex and identify several distinct but spatially overlapping subpopulations with characteristic activity patterns during reach-to-grasp behavior.