Dopamine Is Required for the Neural Representation and Control of Movement Vigor

• Published in: Cell Vol. 162; no. 6; pp. 1418 - 1430
• Main Authors: Panigrahi, Babita, Martin, Kathleen A., Li, Yi, Graves, Austin R., Vollmer, Alison, Olson, Lars, Mensh, Brett D., Karpova, Alla Y., Dudman, Joshua T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.09.2015
• Subjects: Animals; Basal Ganglia - metabolism; Disease Models, Animal; Dopamine - metabolism; Hypokinesia - metabolism; Hypokinesia - physiopathology; Medicin och hälsovetenskap; Mesencephalon - metabolism; Mice; Muscle, Skeletal - physiology; Parkinson Disease - metabolism; Parkinson Disease - physiopathology
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2015.08.014

Progressive depletion of midbrain dopamine neurons (PDD) is associated with deficits in the initiation, speed, and fluidity of voluntary movement. Models of basal ganglia function focus on initiation deficits; however, it is unclear how they account for deficits in the speed or amplitude of movement (vigor). Using an effort-based operant conditioning task for head-fixed mice, we discovered distinct functional classes of neurons in the dorsal striatum that represent movement vigor. Mice with PDD exhibited a progressive reduction in vigor, along with a selective impairment of its neural representation in striatum. Restoration of dopaminergic tone with a synthetic precursor ameliorated deficits in movement vigor and its neural representation, while suppression of striatal activity during movement was sufficient to reduce vigor. Thus, dopaminergic input to the dorsal striatum is indispensable for the emergence of striatal activity that mediates adaptive changes in movement vigor. These results suggest refined intervention strategies for Parkinson’s disease. [Display omitted] •A mouse model of Parkinson’s disease produces a persistent reduction in effort•The neural representation of movement vigor in striatum requires dopamine•Acute suppression of striatal activity during execution enervates movement•Dopamine repletion is sufficient to restore striatal activity and invigorate movement Movement vigor, reduced in Parkinson’s disease, is regulated by dopamine-dependent activity in the striatum.