Subtype-specific plasticity of inhibitory circuits in motor cortex during motor learning

Motor skill learning induces long-lasting reorganization of dendritic spines, major sites of excitatory synapses, in the motor cortex. However, mechanisms that regulate these excitatory synaptic changes remain poorly understood. Here using in vivo two-photon imaging in awake mice, we found that learning-induced spine reorganization of L2/3 excitatory neurons occurs in the distal branches of their apical dendrites in L1 but not in the perisomatic dendrites. This compartment-specific spine reorganization coincided with subtype-specific plasticity of local inhibitory circuits. Somatostatin-expressing inhibitory neurons (SOM-INs) that mainly inhibit distal dendrites of excitatory neurons showed a decrease in axonal boutons immediately after the training begins, whereas parvalbumin-expressing inhibitory neurons (PV-INs) that mainly inhibit perisomatic regions of excitatory neurons exhibited a gradual increase in the axonal boutons during training. Optogenetic enhancement and suppression of SOM-IN activity during training destabilized and hyper-stabilized spines, respectively, and both manipulations impaired the learning of stereotyped movements. Our results identify SOM inhibition of distal dendrites as a key regulator of learning-related changes in excitatory synapses and the acquisition of motor skills.