Dopamine receptor-expressing neurons are differently distributed throughout layers of the motor cortex to control dexterity

Abstract

The motor cortex comprises the primary descending circuits for flexible control of voluntary movements and is critically involved in motor skill learning. Motor skill learning is impaired in patients with Parkinsons disease, but the precise mechanisms of motor control and skill learning are still not well understood. Here we have used transgenic mice, electrophysiology, in situ hybridization and neural tract-tracing methods to target genetically defined cell types expressing D1 and D2 dopamine receptors (D1+ and D2+, respectively) in the motor cortex. We observed that D1+ and D2+ neurons are organized in highly segregated, non-overlapping populations. Moreover, based on ex vivo patch-clamp recordings, we showed that D1+ and D2+ cells have distinct morphological and electrophysiological properties. Finally, we observed that chemogenetic inhibition of D2+, but not D1+ neurons, disrupts skilled forelimb reaching in adult mice. Overall, these results demonstrate that dopamine receptor-expressing cells in the motor cortex are highly segregated and play a specialized role in manual dexterity.