title: Learning-related fine-scale specificity imaged in motor cortex circuits of behaving mice.
abstract: Cortical neurons form specific circuits, 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 cortex. 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 odour. Mice routinely showed significant learning within the first behavioural session and across sessions. Microstimulation and trans-synaptic tracing 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 approximately 150 mum) 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.
authors.affiliation: Janelia Farm Research Campus, HHMI, Ashburn, Virginia 20147, USA. komiyamat@janelia.hhmi.org
authors.forename: Takaki
authors.initials: T
authors.lastname: Komiyama
authors.forename: Takashi R
authors.initials: TR
authors.lastname: Sato
authors.forename: Daniel H
authors.initials: DH
authors.lastname: O'Connor
authors.forename: Ying-Xin
authors.initials: YX
authors.lastname: Zhang
authors.forename: Daniel
authors.initials: D
authors.lastname: Huber
authors.forename: Bryan M
authors.initials: BM
authors.lastname: Hooks
authors.forename: Mariano
authors.initials: M
authors.lastname: Gabitto
authors.forename: Karel
authors.initials: K
authors.lastname: Svoboda
mesh_terms: D000818:Animals; D001370:Axonal Transport; D001522:Behavior, Animal / Q000502:physiology*; D002755:Choice Behavior / Q000502:physiology; D007858:Learning / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009044:Motor Cortex / Q000166:cytology* / Q000502:physiology*; D009046:Motor Neurons / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology*; D009812:Odorants / Q000032:analysis; D017966:Pyramidal Cells / Q000502:physiology; D012201:Reward; D013268:Stimulation, Chemical; D013997:Time Factors; D014059:Tongue / Q000166:cytology / Q000294:innervation / Q000502:physiology