title: Dopamine Is Required for the Neural Representation and Control of Movement Vigor.
abstract: 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.
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
authors.forename: Babita
authors.initials: B
authors.lastname: Panigrahi
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Martin
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
authors.forename: Austin R
authors.initials: AR
authors.lastname: Graves
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Vollmer
authors.affiliation: Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Olson
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
authors.forename: Brett D
authors.initials: BD
authors.lastname: Mensh
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
authors.forename: Alla Y
authors.initials: AY
authors.lastname: Karpova
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. Electronic address: dudmanj@janelia.hhmi.org.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Dudman
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018476:Hypokinesia / Q000378:metabolism / Q000503:physiopathology; D008636:Mesencephalon / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000502:physiology; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D004298:Dopamine