PT - JOURNAL ARTICLE AU - Xu An AU - Katherine Matho AU - Yi Li AU - Hemanth Mohan AU - X. Hermione Xu AU - Ian Q. Whishaw AU - Adam Kepecs AU - Z. Josh Huang TI - A cortical circuit for orchestrating oromanual food manipulation AID - 10.1101/2022.12.03.518964 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.12.03.518964 4099 - http://biorxiv.org/content/early/2022/12/03/2022.12.03.518964.short 4100 - http://biorxiv.org/content/early/2022/12/03/2022.12.03.518964.full AB - 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 StatementThe authors have declared no competing interest.ACAdanterior cingulate area, dorsal partAIdagranular insular area, dorsal partAPNanterior pretectal nucleusCBcerebellumCEAccentral amygdalar nucleus, capsular partCLcentral lateral nucleus of the thalamusCPcaudoputamenFRPfrontal poleGPeglobus pallidus, external segmentGPiglobus pallidus, internal segmentGRNgigantocellular reticular nucleusGUgustatory areasHPFhippocampal formationHYhypothalamusIRNintermediate reticular nucleusMDmediodorsal nucleus of the thalamusMdDmedullary reticular nucleus, dorsal partMDRNmedullary reticular nucleusMdVmedullary reticular nucleus, ventral partMOpprimary motor areaMOssecondary motor areaMRNmidbrain reticular nucleusOLFolfactory areasORBlorbital area, lateral partPALpallidumPARNparvicellular reticular nucleusPCNparacentral nucleusPFparafascicular nucleusPGpontine grayPLprelimbic areaPOposterior complex of the thalamusPPNpedunculopontine nucleusPSVprincipal sensory nucleus of the trigeminalpyxpyramidal decussationRSPaglretrosplenial area, lateral agranular partRSPdretrosplenial area, dorsal partSCsuperior colliculusSCmsuperior colliculus, motor relatedSIsubstantia innominataSMTsubmedial nucleus of the thalamusspcortical subplateSpdspinal cordSPVspinal nucleus of the trigeminalSSp-bfdprimary somatosensory area, barrel fieldSSp-llprimary somatosensory area, lower limbSSp-mprimary somatosensory area, mouthSSp-nprimary somatosensory area, noseSSp-trprimary somatosensory area, trunkSSp-ulprimary somatosensory area, upper limbSSp-unprimary somatosensory area, unassignedSSssecondary somatosensory areaSTNsubthalamic nucleusSTRstriatumVmotor nucleus of trigeminalVALventral anterior-lateral complex of the thalamusVIIfacial motor nucleusVISaanterior areaVISamanteromedial visual areaVISCvisceral areaVISpprimary visual areaVISpmposteromedial visual areaVISrlrostrolateral visual areaVMventral medial nucleus of the thalamusVPMventral posteromedial nucleus of the thalamusZIzona incerta