biostudies-literatureXu DNINDS NIH HHS464-469https://www.ebi.ac.uk/biostudies/studies/S-EPMC9109820biostudies-literatureUnknown603(7901)The brain generates complex sequences of movements that can be flexibly configured based on behavioural context or real-time sensory feedback¹, but how this occurs is not fully understood. Here we developed a 'sequence licking' task in which mice directed their tongue to a target that moved through a series of locations. Mice could rapidly branch the sequence online based on tactile feedback. Closed-loop optogenetics and electrophysiology revealed that the tongue and jaw regions of the primary somatosensory (S1TJ) and motor (M1TJ) cortices² encoded and controlled tongue kinematics at the level of individual licks. By contrast, the tongue 'premotor' (anterolateral motor) cortex^3-10 encoded latent variables including intended lick angle, sequence identity and progress towards the reward that marked successful sequence execution. Movement-nonspecific sequence branching signals occurred in the anterolateral motor cortex and M1TJ. Our results reveal a set of key cortical areas for flexible and context-informed sequence generation.NatureCortical processing of flexible and context-dependent sensorimotor sequences.PMC9109820R01 NS104834R01 NS089652P30 NS050274Delgado AMXu DDong MChen YZhang LO'Connor DHHughes NCfalseCortical processing of flexible and context-dependent sensorimotor sequences.The brain generates complex sequences of movements that can be flexibly configured based on behavioural context or real-time sensory feedback¹, but how this occurs is not fully understood. Here we developed a 'sequence licking' task in which mice directed their tongue to a target that moved through a series of locations. Mice could rapidly branch the sequence online based on tactile feedback. Closed-loop optogenetics and electrophysiology revealed that the tongue and jaw regions of the primary somatosensory (S1TJ) and motor (M1TJ) cortices² encoded and controlled tongue kinematics at the level of individual licks. By contrast, the tongue 'premotor' (anterolateral motor) cortex^3-10 encoded latent variables including intended lick angle, sequence identity and progress towards the reward that marked successful sequence execution. Movement-nonspecific sequence branching signals occurred in the anterolateral motor cortex and M1TJ. Our results reveal a set of key cortical areas for flexible and context-informed sequence generation.2022-01-01T00:00:00Z2022 Mar2025-04-05T16:10:10.47Z2025-04-05T16:10:10.47ZS-EPMC91098203526479310.1038/s41586-022-04478-7