Preliminary evidence indicates that dopamine given by mouth facilitates the learning of motor skills and improves the recovery of movement after stroke. The mechanism of these phenomena is unknown. Here, we describe a mechanism by demonstrating in rat that dopaminergic terminals and receptors in primary motor cortex (M1) enable motor skill learning and enhance M1 synaptic plasticity. Elimination of dopaminergic terminals in M1 specifically impaired motor skill acquisition, which was restored upon DA substitution. Execution of a previously acquired skill was unaffected. Reversible blockade of M1 D1 and D2 receptors temporarily impaired skill acquisition but not execution, and reduced long-term potentiation (LTP) within M1, a form of synaptic plasticity critically involved in skill learning. These findings identify a behavioral and functional role of dopaminergic signaling in M1. DA in M1 optimizes the learning of a novel motor skill.

Functional imaging studies in humans and electrophysiological data in animals suggest that cortico-striatal circuits undergo plastic modifications during motor skill learning. In motor cortex and hippocampus circuit plasticity can be prevented by protein synthesis inhibition (PSI) which can interfere with certain forms learning. Here, the hypothesis was tested that inducing PSI in the dorsal striatum by bilateral intrastriatal injection of anisomycin (ANI) in rats interferes with learning a precision forelimb reaching task. Injecting ANI shortly after training on days 1 and 2 during 4 days of daily practice (n=14) led to a significant impairment of motor skill learning as compared with vehicle-injected controls (n=15, p=0.033). ANI did not affect the animals' motivation as measured by intertrial latencies. Also, ANI did not affect reaching performance once learning was completed and performance reached a plateau. These findings demonstrate that PSI in the dorsal striatum after training impairs the acquisition of a novel motor skill. The results support the notion that plasticity in basal ganglia circuits, mediated by protein synthesis, contributes to motor skill learning.