Dopaminergic Projections from Midbrain to Primary Motor Cortex Mediate Motor Skill Learning
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The nigrostriatal system receives projections from the mesolimbic system, which may interact with the motor system, including the primary motor cortex, via other direct and indirect pathways.
“Importantly, the latter system receives projections from the former (Draganski,B.,Kherif, F., Kloppel, S.,Cook, P. A.,Alexander,D.C., Parker et al., 2008;Schmidt, Lebreton, Clery-Melin, Daunizeau, & Pessiglioni, 2012;Yin, Ostlund, Balleine, 2008), which may interact with the motor system, including the primary motor cortex, via other direct and indirect pathways (Hosp, Pekanovic, Rioult-Pedotti, &”
From Optimizing performance through intrinsic motivation and attention for learning: The OPTIMAL theory of motor learning (2016) · cites this paper as Hosp et al., 2011
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
AChE-stained horizontal sections of the rat brain in stereotaxic coordinates
Paxinos, G., WATSON, C. R. R., & Emson, P. C. (1980) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(80)90021-7 · Cited by 4,497 · see citing works
Swanson, L. W. (1982) · Brain Research Bulletin · doi:10.1016/0361-9230(82)90145-9 · Cited by 1,718 · see citing works
Behavioral Theories and the Neurophysiology of Reward
Schultz, W. (2006) · Annual Review of Psychology · doi:10.1146/annurev.psych.56.091103.070229 · Cited by 1,637 · see citing works
Ikemoto, S. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.05.004 · Cited by 1,477 · see citing works
Nudo, R. J., Milliken, G. W., Jenkins, W., & Merzenich, M. M. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-02-00785.1996 · Cited by 1,416 · see citing works
Schultz, W. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.03.007 · Cited by 1,028 · see citing works
Learning-Induced LTP in Neocortex
Rioult-Pedotti, M.-S., Friedman, D. J., & Donoghue, J. P. (2000) · Science · doi:10.1126/science.290.5491.533 · Cited by 1,014 · see citing works
Self-citationFunctional Reorganization of the Rat Motor Cortex Following Motor Skill Learning
Kleim, J. A., Barbay, S., & Nudo, R. J. (1998) · Journal of Neurophysiology · doi:10.1152/jn.1998.80.6.3321 · Cited by 806 · see citing works
The organization of the rat motor cortex: A microstimulation mapping study
Neafsey, E. J., Bold, E. L., HAAS, G., Hurley-Gius, K. M., Quirk, G. J., Sievert, C. F., & Terreberry, R. R. (1986) · Brain Research · doi:10.1016/s0006-8993(86)80191-3 · Cited by 705 · see citing works
Synaptogenesis and FOS Expression in the Motor Cortex of the Adult Rat after Motor Skill Learning
Kleim, J. A., Lussnig, E., Schwarz, E. R., Comery, T. A., & Greenough, W. T. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-14-04529.1996 · Cited by 539 · see citing works
Mesencephalic dopamine neurons projecting to neocortex
Lindvall, O., Björklund, A., Moore, R. Y., & Stenevi, U. (1974) · Brain Research · doi:10.1016/0006-8993(74)90947-0 · Cited by 504 · see citing works
Widespread origin of the primate mesofrontal dopamine system.
Williams, S. M., & Goldman-Rakic, P. (1998) · Cerebral Cortex · doi:10.1093/cercor/8.4.321 · Cited by 481 · see citing works
Whishaw, I. Q., & Pellis, S. M. (1990) · Behavioural Brain Research · doi:10.1016/0166-4328(90)90053-h · Cited by 424 · see citing works
Guzowski, J. F. (2002) · Hippocampus · doi:10.1002/hipo.10010 · Cited by 392 · see citing works
Dopamine in Motor Cortex Is Necessary for Skill Learning and Synaptic Plasticity
Molina-Luna, K., Pekanovic, A., Röhrich, S., Hertler, B., Schubring-Giese, M., Rioult-Pedotti, M.-S., & Luft, A. R. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007082 · Cited by 350 · see citing works
Self-citationRegional and laminar density of the dopamine innervation in adult rat cerebral cortex
Descarries, L., Lemay, B., Doucet, G., & Berger, B. (1987) · Neuroscience · doi:10.1016/0306-4522(87)90038-8 · Cited by 341 · see citing works
Midbrain dopaminergic neurons (nuclei A8, A9, and A10): Three‐dimensional reconstruction in the rat
German, D. C., & Manaye, K. F. (1993) · The Journal of Comparative Neurology · doi:10.1002/cne.903310302 · Cited by 255 · see citing works
Pirot, S., Godbout, R., Mantz, J., Tassin, J., Glowinski, J., & Thierry, A. M. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90362-6 · Cited by 237 · see citing works
Short and long-term motor skill learning in an accelerated rotarod training paradigm
Buitrago, M. M. (2004) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2004.01.001 · Cited by 213 · see citing works
Telencephalic Projections of the A8 Dopamine Cell Group
Deutch, A. Y., Goldstein, M., Baldino, F., & Roth, R. H. (1988) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1988.tb42095.x · Cited by 205 · see citing works
Gaspar, P., Stepniewska, I., & Kaas, J. H. (1992) · The Journal of Comparative Neurology · doi:10.1002/cne.903250102 · Cited by 180 · see citing works
Substantia nigra and ventral tegmental area projections to cortex: Topography and collateralization
Loughlin, S. E., & Fallon, J. H. (1984) · Neuroscience · doi:10.1016/0306-4522(84)90034-4 · Cited by 163 · see citing works
Motor Skill Learning Depends on Protein Synthesis in Motor Cortex after Training
Luft, A. R., Buitrago, M. M., Ringer, T. M., DICHGANS, J., & Schulz, J. B. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1034-04.2004 · Cited by 146 · see citing works
Self-citationPlasticity of the Synaptic Modification Range
Rioult-Pedotti, M.-S., Donoghue, J. P., & Dunaevsky, A. (2007) · Journal of Neurophysiology · doi:10.1152/jn.00164.2007 · Cited by 137 · see citing works
Self-citationExtrastriatal monoamine neuron function in Parkinson’s disease: An 18F-dopa PET study
Moore, R. Y., Whone, A. L., & Brooks, D. J. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.09.004 · Cited by 136 · see citing works
Wang, J. Q., Smith, A. J. W., & McGinty, J. F. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00100-w · Cited by 136 · see citing works
Specific A10 Dopaminergic Nuclei in the Midbrain Degenerate in Parkinson's Disease
McRitchie, D. A., Cartwright, H., & Halliday, G. M. (1997) · Experimental Neurology · doi:10.1006/exnr.1997.6418 · Cited by 135 · see citing works
Frith, C., Bloxham, C. A., & Carpenter, K. N. (1986) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.49.6.661 · Cited by 128 · see citing works
Motor learning transiently changes cortical somatotopy
Molina-Luna, K., Hertler, B., Buitrago, M. M., & Luft, A. R. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.11.018 · Cited by 116 · see citing works
Self-citationRole of the mesotelencephalic dopamine system in learning and memory processes in the rat
Hefco, V., Yamada, K., Hefco, A., Hriţcu, L., Tiron, A., & Nabeshima, T. (2003) · European Journal of Pharmacology · doi:10.1016/s0014-2999(03)02115-0 · Cited by 115 · see citing works
Verschueren, S. M. P., Swinnen, S. P., Dom, R., & De Weerdt, W. (1997) · Experimental Brain Research · doi:10.1007/pl00005602 · Cited by 96 · see citing works
Dopaminergic signals in primary motor cortex
Luft, A. R., & Schwarz, S. (2009) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2009.05.004 · Cited by 92 · see citing works
Self-citationBuitrago, M. M., Ringer, T. M., Schulz, J. B., DICHGANS, J., & Luft, A. R. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.04.025 · Cited by 76 · see citing works
Self-citationThe nigrostriatal DA pathway and Parkinson’s disease
Fuxé, K., Manger, P. R., Genedani, S., & Agnati, L. F. (2006) · Springer eBooks · doi:10.1007/978-3-211-45295-0_13 · Cited by 52 · see citing works
The organization of dopaminergic and non-dopaminergic mesencephalo-cortical neurons in the rat
Albanese, A., & Bentivoglio, M. (1982) · Brain Research · doi:10.1016/0006-8993(82)90117-2 · Cited by 50 · see citing works
Mao, L., & Wang, J. Q. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02495.x · Cited by 47 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Principles of sensorimotor learning
Wolpert, D. M., Diedrichsen, J., & Flanagan, J. R. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3112 · Cited by 1,391 · see citing works
Wulf, G., & Lewthwaite, R. (2016) · Psychonomic Bulletin & Review · doi:10.3758/s13423-015-0999-9 · Cited by 1,238 · see citing works
Huang, V. S., Haith, A., Mazzoni, P., & Krakauer, J. W. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.012 · Cited by 472 · see citing works
Model-Based and Model-Free Mechanisms of Human Motor Learning
Haith, A. M., & Krakauer, J. W. (2013) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4614-5465-6_1 · Cited by 263 · see citing works
Circuit Mechanisms of Sensorimotor Learning
Makino, H., Hwang, E. J., Hedrick, N. G., & Komiyama, T. (2016) · Neuron · doi:10.1016/j.neuron.2016.10.029 · Cited by 228 · see citing works
Motor learning in neurological rehabilitation
Levin, M. F., & Demers, M. (2021) · Disability and Rehabilitation · doi:10.1080/09638288.2020.1752317 · Cited by 198 · see citing works
The role of prediction in social neuroscience
Brown, E. C., & Brüne, M. (2012) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2012.00147 · Cited by 190 · see citing works
Motor primitives in space and time via targeted gain modulation in cortical networks
Stroud, J. P., Porter, M. A., Hennequin, G., & Vogels, T. P. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0276-0 · Cited by 119 · see citing works
Cell-based reporters reveal in vivo dynamics of dopamine and norepinephrine release in murine cortex
Muller, A., Joseph, V., Slesinger, P. A., & Kleinfeld, D. (2014) · Nature Methods · doi:10.1038/nmeth.3151 · Cited by 139 · see citing works
Cortical–hippocampal coupling during manifold exploration in motor cortex
Kim, J., Joshi, A., Frank, L., & Ganguly, K. (2023) · Nature · doi:10.1038/s41586-022-05533-z · Cited by 77 · see citing works
Learning to Produce Syllabic Speech Sounds via Reward-Modulated Neural Plasticity
Warlaumont, A. S., & Finnegan, M. K. (2016) · PLOS ONE · doi:10.1371/journal.pone.0145096 · Cited by 71 · see citing works
The rewarding value of good motor performance in the context of monetary incentives
Lutz, K., Pedroni, A., Nadig, K., Luechinger, R., & Jäncke, L. (2012) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2012.03.030 · Cited by 40 · see citing works
Concurrent TMS to the primary motor cortex augments slow motor learning
Narayana, S., Zhang, W., Rogers, W., Strickland, C., Franklin, C., Lancaster, J. L., & Fox, P. T. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2013.07.024 · Cited by 41 · see citing works
Pharmacological Manipulation of Kv7 Channels as a New Therapeutic Tool for Multiple Brain Disorders
Vigil, F. A., Carver, C. M., & Shapiro, M. S. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00688 · Cited by 36 · see citing works
- Authors
- Hosp, J. A., Pekanovic, A., Rioult-Pedotti, M. S., & Luft, A. R.
- Affiliations
- University of Zurich (CH)
- Johns Hopkins University (US)
- Corresponding author
- Luft, Andreas R.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-02-16
- Volume
- 31
- Issue
- 7
- Pages
- 2481-2487
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6623715
- OpenAlex
- W2019256317
- Cited by
- 354
- References
- 36
- Citations by year
- 2026: 18 · 2025: 16 · 2024: 31 · 2023: 19 · 2022: 31 · 2021: 22 · 2020: 21 · 2019: 28 · 2018: 21 · 2017: 27 · 2016: 20 · 2015: 20 · 2014: 25 · 2013: 21 · 2012: 20
- FWCI
- 12.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- dopaminergic pathways, ventral tegmental area, primary motor cortex, motor skill learning, dopamine D1 receptor, dopamine D2 receptor, c-fos, cellular plasticity, reward signaling, forelimb reaching, levodopa, retrograde tracing
- MeSH terms
- Afferent Pathways, Amidines, Animals, Behavior, Animal, Benzazepines, Conditioning, Operant, Dopamine, Drug Combinations, Gene Expression Regulation, Male, Motor Cortex, Motor Skills, Neurons, Reaction Time, Tyrosine 3-Monooxygenase, Oxidopamine, Proto-Oncogene Proteins c-fos, Ventral Tegmental Area, Dopamine Antagonists, Adrenergic Agents, Rats, Long-Evans, Raclopride, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review