Motor execution, but not learning, improves upon increased layer 5 specific Martinotti cell excitation

Abstract

AbstractDuring motor activity and motor learning, pyramidal cells in the motor cortex receive inputs from local interneurons as well as deeper structures. Layer 5 pyramidal tract pyramidal cells in the primary motor cortex then feed commands to spinal circuits for motor execution. Using monosynaptic retrograde viral tracing, we show that layer 5 Chrna2 Martinotti cells, which selectively target pyramidal tract pyramidal cells, receive direct input from thalamic and cholinergic nuclei. Further their genetic ablation results in disturbed fine motor functions. Using calcium imaging combined with chemogenetics, we show that activation of layer 5 Chrna2 Martinotti cells during training reduces pyramidal cell tuning, temporal patterning and assembly reconfiguration while not affecting motor learning success rates. However, in mice that had already learned a reach-and-grasp (prehension) task, Chrna2 Martinotti cell activation resulted in improved prehension. This work indicates that activation of Chrna2 Martinotti cells reduces pyramidal cell assembly plasticity during learning, facilitating preservation of already acquired motor skills.