A cortical circuit for orchestrating oromanual food manipulation

ABSTRACT The seamless coordination of hands and mouth—whether in humans eating corn on the cob or mice extracting sunflower seeds—represents one of evolution’s most sophisticated motor achievements. Whereas spinal and brainstem circuits implement basic forelimb and orofacial actions, whether there is a specialized cortical circuit that assembles these actions to enable skilled oromanual manipulation remains unclear. Here, we discover a cortical area and its cell-type-specific circuitry that govern oromanual food manipulation in mice. An optogenetic screen of cortical areas and projection neuron types identified a rostral forelimb-orofacial area (RFO), wherein activation of pyramidal tract (PT Fezf2 ) and intratelencephalic (IT PlxnD1 ) neurons induced concerted posture, forelimb and orofacial movements resembling eating. In a freely moving pasta-eating behavior, pharmacological RFO inactivation impaired the sitting posture, hand recruitment, and oromanual coordination in pasta eating. RFO PT Fezf2 and IT PlxnD1 activity was closely correlated with oromanual pasta manipulation and hand-assisted biting. Optogenetic inhibition revealed that PTs Fezf2 regulate dexterous hand and mouth movements while ITs PlxnD1 play a more prominent role in oromanual coordination. RFO forms the hub of an extensive network, with reciprocal connections to cortical forelimb and orofacial sensorimotor areas, as well as insular and visceral areas. Within this cortical network, RFO PTs Fezf2 project unilaterally to multiple subcortical, brainstem and spinal areas associated with forelimb and orofacial control, while ITs PlxnD1 project bilaterally to the entire network and the ventrolateral striatum, and can mediate concurrent forelimb and mouth movement in part through their striatal projection. Together, these findings uncover the cell-type-specific implementation of a cortical circuit that orchestrates oromanual manipulation, essential for skilled feeding.