# A cortical circuit for orchestrating oromanual food manipulation

## TL;DR

The study identifies a specific brain region and its circuitry that coordinates hand and mouth movements for eating in mice.

## Contribution

The discovery of a cortical area (RFO) and its cell-type-specific circuitry that orchestrates oromanual food manipulation in mice.

## Key findings

- Activation of RFO neurons induces coordinated posture, limb, and orofacial movements resembling eating.
- Pharmacological inactivation of RFO impairs posture, hand use, and coordination during pasta eating.
- RFO PT Fezf2 and IT PlxnD1 neurons regulate hand-mouth coordination through distinct subcortical projections.

## 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.