title: Dopaminergic projections from midbrain to primary motor cortex mediate motor skill learning.
abstract: The primary motor cortex (M1) of the rat contains dopaminergic terminals. The origin of this dopaminergic projection and its functional role for movement are obscure. Other areas of cortex receive dopaminergic projections from the ventral tegmental area (VTA) of the midbrain, and these projections are involved in learning phenomena. We therefore hypothesized that M1 receives a dopaminergic projection from VTA and that this projection mediates the learning of a motor skill by inducing cellular plasticity events in M1. Retrograde tracing from M1 of Long-Evans rats in conjunction with tyrosine hydroxylase immunohistochemistry identified dopaminergic cell bodies in VTA. Electrical stimulation of VTA induced expression of the immediate-early gene c-fos in M1, which was blocked by intracortical injections of D(1) and D(2) antagonists. Destroying VTA dopaminergic neurons prevented the improvements in forelimb reaching seen in controls during daily training. Learning recovered on administration of levodopa into the M1 of VTA-lesioned animals. Lesioning VTA did not affect performance of an already learned skill, hence, left movement execution intact. These findings provide evidence that dopaminergic terminals in M1 originate in VTA, contribute to M1 plasticity, and are necessary for successful motor skill learning. Because VTA dopaminergic neurons are known to signal rewards, the VTA-to-M1 projection is a candidate for relaying reward information that could directly support the encoding of a motor skill within M1.
authors.affiliation: Clinical Neurorehabilitation, Department of Neurology, University of Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Jonas A
authors.initials: JA
authors.lastname: Hosp
authors.forename: Ana
authors.initials: A
authors.lastname: Pekanovic
authors.forename: Mengia S
authors.initials: MS
authors.lastname: Rioult-Pedotti
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Luft
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000578:Amidines / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001552:Benzazepines / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004338:Drug Combinations; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology*; D009048:Motor Skills / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000166:cytology* / Q000293:injuries / Q000502:physiology
chemical_list: D018663:Adrenergic Agents; D000578:Amidines; D001552:Benzazepines; D018492:Dopamine Antagonists; D004338:Drug Combinations; D016760:Proto-Oncogene Proteins c-fos; C534628:SCH 23390; C031455:diamidino compound 253-50; D020891:Raclopride; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine