A cortical circuit for orchestrating oromanual food manipulation

Cooperative forelimb and mouth movements during eating contribute to diet selection among vertebrates including the oromanual manipulatory skills in rodents and primates. Whereas spinal and brainstem circuits implement forelimb and orofacial actions, whether there is a specialized cortical circuit that flexibly assembles these to achieve cross-body and oromanual coordination for skilled manipulation remains unclear. Here we discover a cortical region and its cell-type-specific circuitry that orchestrates body postures and oromanual coordination for 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 (PTFezf2) and intratelencephalic (ITPlxnD1) neurons induced concurrent posture, forelimb and orofacial eating-like movements. In a pasta-eating behavior, RFO PTFezf2 and ITPlxnD1 activity were closely correlated with picking up the pasta, adopting a sitting posture, oromanual manipulation, and hand-assisted biting. RFO inactivation and inhibition of RFO PTsFezf2 and ITsPlxnD1 impaired posture and oromanual coordination, leading to deficient pasta manipulation and biting. RFO is reciprocally connected to forelimb and orofacial sensorimotor areas as well as insular and visceral areas. Within this network, ITsPlxnD1project bilaterally to the entire network and the ventrolateral striatum and PTsFezf2 project to multiple subcortical areas associated with forelimb and orofacial control. These results suggest that ITsPlxnD1 select and coordinate the feeding program involving multiple body parts and PTsFezf2 implement the fine details of movements. Our study reveals a neural circuit basis of hand-mouth coordination for object manipulation. ### Competing Interest Statement The authors have declared no competing interest. * ACAd : anterior cingulate area, dorsal part AId : agranular insular area, dorsal part APN : anterior pretectal nucleus CB : cerebellum CEAc : central amygdalar nucleus, capsular part CL : central lateral nucleus of the thalamus CP : caudoputamen FRP : frontal pole GPe : globus pallidus, external segment GPi : globus pallidus, internal segment GRN : gigantocellular reticular nucleus GU : gustatory areas HPF : hippocampal formation HY : hypothalamus IRN : intermediate reticular nucleus MD : mediodorsal nucleus of the thalamus MdD : medullary reticular nucleus, dorsal part MDRN : medullary reticular nucleus MdV : medullary reticular nucleus, ventral part MOp : primary motor area MOs : secondary motor area MRN : midbrain reticular nucleus OLF : olfactory areas ORBl : orbital area, lateral part PAL : pallidum PARN : parvicellular reticular nucleus PCN : paracentral nucleus PF : parafascicular nucleus PG : pontine gray PL : prelimbic area PO : posterior complex of the thalamus PPN : pedunculopontine nucleus PSV : principal sensory nucleus of the trigeminal pyx : pyramidal decussation RSPagl : retrosplenial area, lateral agranular part RSPd : retrosplenial area, dorsal part SC : superior colliculus SCm : superior colliculus, motor related SI : substantia innominata SMT : submedial nucleus of the thalamus sp : cortical subplate Spd : spinal cord SPV : spinal nucleus of the trigeminal SSp-bfd : primary somatosensory area, barrel field SSp-ll : primary somatosensory area, lower limb SSp-m : primary somatosensory area, mouth SSp-n : primary somatosensory area, nose SSp-tr : primary somatosensory area, trunk SSp-ul : primary somatosensory area, upper limb SSp-un : primary somatosensory area, unassigned SSs : secondary somatosensory area STN : subthalamic nucleus STR : striatum V : motor nucleus of trigeminal VAL : ventral anterior-lateral complex of the thalamus VII : facial motor nucleus VISa : anterior area VISam : anteromedial visual area VISC : visceral area VISp : primary visual area VISpm : posteromedial visual area VISrl : rostrolateral visual area VM : ventral medial nucleus of the thalamus VPM : ventral posteromedial nucleus of the thalamus ZI : zona incerta