ArticleProceedings of the National Academy of Sciences of the United States of America2023
Learning critically drives parkinsonian motor deficits through imbalanced striatal pathway recruitment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Braking Parkinson's progression: the hypothetical druggable role of striatal parvalbumin interneurons.NPJ Parkinson's disease · 2026Review
- Dopamine 2 receptor ablation from cholinergic neurons attenuates L-DOPA induced dyskinesias.Frontiers in aging neuroscience · 2026Article
- Voluntary exercise increases striatal dopamine release and improves motor performance in aging mice.NPJ Parkinson's disease · 2025Article
- State-dependent modulation of spiny projection neurons controls levodopa-induced dyskinesia in a mouse model of Parkinson's disease.Science advances · 2025Article
- Subsecond dopamine fluctuations do not specify the vigor of ongoing actions.Nature neuroscience · 2025Article
- Neurodegenerative Disease Movement Disorders and Dorsal Striatum-Mediated Imbalance of Habitual Motor Sequences.Molecular neurobiology · 2025Review
- Differential modulation of movement speed with state-dependent deep brain stimulation in Parkinson's disease.Science advances · 2025Article
- Disease-Modifying Trials in Treated Parkinson's Disease: "Stable Treated" Does Not Equate with Biological Stability.Movement disorders : official journal of the Movement Disorder Society · 2025Review
- Movement-related activity in the internal globus pallidus of the parkinsonian macaque.Journal of neurophysiology · 2025Article
- Erasing "bad memories": reversing aberrant synaptic plasticity as therapy for neurological and psychiatric disorders.Molecular psychiatry · 2025Review
- Article
- Striatal Dopamine Actions and Movement: Inferences from Parkinson Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Developing algorithmic psychiatry via multi-level spanning computational models.Cell reports. Medicine · 2025Review
- Article
- Histamine Modulation of the Basal Ganglia Circuitry in the Motor Symptoms of Parkinson's Disease.CNS neuroscience & therapeutics · 2025Review
- State-dependent modulation of spiny projection neurons controls levodopa-induced dyskinesia in a mouse model of Parkinson's disease.bioRxiv : the preprint server for biology · 2025Article
- Adaptive chunking improves effective working memory capacity in a prefrontal cortex and basal ganglia circuit.bioRxiv : the preprint server for biology · 2024Article
- Ethological computational psychiatry: Challenges and opportunities.Current opinion in neurobiology · 2024Review
- Disuse-driven plasticity in the human thalamus and putamen.bioRxiv : the preprint server for biology · 2024Article
- Proceedings of the 11th Annual Deep Brain Stimulation Think Tank: pushing the forefront of neuromodulation with functional network mapping, biomarkers for adaptive DBS, bioethical dilemmas, AI-guided neuromodulation, and translational advancements.Frontiers in human neuroscience · 2024Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Dopamine (DA) loss in Parkinson's disease (PD) causes debilitating motor deficits. However, dopamine is also widely linked to reward prediction and learning, and the contribution of dopamine-dependent learning to movements that are impaired in PD-which often do not lead to explicit rewards-is unclear. Here, we used two distinct motor tasks to dissociate dopamine's acute motoric effects vs. its long-lasting, learning-mediated effects. In dopamine-depleted mice, motor task performance gradually worsened with task exposure. Task experience was critical, as mice that remained in the home cage during the same period were relatively unimpaired when subsequently probed on the task. Repeated dopamine replacement treatments acutely rescued deficits and gradually induced long-term rescue that persisted despite treatment withdrawal. Surprisingly, both long-term rescue and parkinsonian performance decline were task specific, implicating dopamine-dependent learning. D1R activation potently induced acute rescue that gradually consolidated into long-term rescue. Conversely, reduced D2R activation potently induced parkinsonian decline. In dopamine-depleted mice, either D1R activation or D2R activation prevented parkinsonian decline, and both restored balanced activation of direct vs. indirect striatal pathways. These findings suggest that reinforcement and maintenance of movements-even movements not leading to explicit rewards-are fundamental functions of dopamine and provide potential mechanisms for the hitherto unexplained "long-duration response" by dopaminergic therapies in PD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.