Cortical neurons form specific circuits1, but the functional structure of this microarchitecture and its relation to behaviour are poorly understood. Two-photon calcium imaging can monitor activity of spatially defined neuronal ensembles in the mammalian cortex2,3,4,5. Here we applied this technique to the motor cortex of mice performing a choice behaviour. Head-fixed mice were trained to lick in response to one of two odours, and to withhold licking for the other odour6,7. Mice routinely showed significant learning within the first behavioural session and across sessions. Microstimulation8,9 and trans-synaptic tracing10,11 identified two non-overlapping candidate tongue motor cortical areas. Inactivating either area impaired voluntary licking. Imaging in layer 2/3 showed neurons with diverse response types in both areas. Activity in approximately half of the imaged neurons distinguished trial types associated with different actions. Many neurons showed modulation coinciding with or preceding the action, consistent with their involvement in motor control. Neurons with different response types were spatially intermingled. Nearby neurons (within ∼150 μm) showed pronounced coincident activity. These temporal correlations increased with learning within and across behavioural sessions, specifically for neuron pairs with similar response types. We propose that correlated activity in specific ensembles of functionally related neurons is a signature of learning-related circuit plasticity. Our findings reveal a fine-scale and dynamic organization of the frontal cortex that probably underlies flexible behaviour.
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We thank D. Rinberg for help with experiments; F. Collman, D. Tank, C. Zuker, T. O’Connor and V. Iyer for help with analysis and imaging software; L. W. Enquist for pseudorabies vectors; W. Denk for help with mechanical design; D. Dombeck, M. Andermann, A. Kerlin and C. Reid for discussions about imaging awake mice; B. Shields, A. Hu and S. Michael for help with histology; A. Arnold for help with imaging; J. Osborne and S. Bassin for machining; L. Luo, Z. Mainen and D. Rinberg for comments on the manuscript; A. C. Gontang for illustration. Supported by Howard Hughes Medical Institute. T.K. is a Helen Hay Whitney Foundation postdoctoral fellow.
Author Contributions T.K. and K.S. conceived the project. T.K. developed and performed most of the experiments. D.H.O. helped to develop head-fixed behaviour. D.H. developed the glass-plug imaging window. Y.-X.Z. and D.H. performed optical stimulation mapping. T.K. and T.R.S. performed electrical stimulation mapping. T.K., B.M.H. and T.R.S. performed PRV tracing. T.K., T.R.S. and K.S. analysed data. M.G. provided a software module for image segmentation. T.K. and K.S. wrote the paper.
This movie shows normal voluntary licking of mice with muscimol injections in the somatosensory cortex.
This movie shows normal voluntary licking of mice with muscimol injections in the anterior-medial cortex.
This movie shows defects in voluntary licking of mice with muscimol injections in alM.
This movie shows defects in voluntary licking of mice with muscimol injections in pmM.