Abstract
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.
Highlights
Levodopa, a stable precursor of dopamine (DA), improves the recovery of movement abilities in disabled stroke survivors when given by mouth before daily physiotherapy sessions [1]
Dopamine terminals in M1 and motor skill learning Motor skill learning was impaired in rats with destroyed M1 dopaminergic terminals in the forelimb area of the primary motor cortex (M1)
Dopaminergic terminals were selectively eliminated by intracortical injection of 6-hydroxydopamine (6-OHDA) into the M1 forelimb area of the hemisphere contralateral to the preferred forelimb in conjunction with desipramine (i.p.) to protect noradrenergic terminals (6-OHDA+D, n = 6)
Summary
A stable precursor of dopamine (DA), improves the recovery of movement abilities in disabled stroke survivors when given by mouth before daily physiotherapy sessions [1]. Plastic adaptations in the brain are partly responsible for such recovery processes [2,3] as well as for learning of a motor skill [4]. Levodopa improves such adaptations in stroke [5] and healthy subjects [6], and its metabolite levels correlate with the effectiveness of skill learning [7]. Skill learning is impaired in patients with Parkinson’s disease in whom the brain’s dopaminergic system degenerates [8]. We present findings suggesting that these phenomena are explained by dopaminergic transmission in primary motor cortex (M1) that enables M1 synaptic plasticity
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