Dopaminergic modulation of striatal function and Parkinson’s disease
Open accessAbstract
The striatum is richly innervated by mesencephalic dopaminergic neurons that modulate a diverse array of cellular and synaptic functions that control goal-directed actions and habits. The loss of this innervation has long been thought to be the principal cause of the cardinal motor symptoms of Parkinson's disease (PD). Moreover, chronic, pharmacological overstimulation of striatal dopamine (DA) receptors is generally viewed as the trigger for levodopa-induced dyskinesia (LID) in late-stage PD patients. Here, we discuss recent advances in our understanding of the relationship between the striatum and DA, particularly as it relates to PD and LID. First, it has become clear that chronic perturbations of DA levels in PD and LID bring about cell type-specific, homeostatic changes in spiny projection neurons (SPNs) that tend to normalize striatal activity. Second, perturbations in DA signaling also bring about non-homeostatic aberrations in synaptic plasticity that contribute to disease symptoms. Third, it has become evident that striatal interneurons are major determinants of network activity and behavior in PD and LID. Finally, recent work examining the activity of SPNs in freely moving animals has revealed that the pathophysiology induced by altered DA signaling is not limited to imbalance in the average spiking in direct and indirect pathways, but involves more nuanced disruptions of neuronal ensemble activity.
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Various conditions including Parkinson's disease and psychiatric disorders are accompanied by striatal dysfunction.
“APOE4 non-carriers demonstrated a distinct pattern of reduced striatal intracellular integrity (caudate RI) with cognitive impairment, which may point to AD-independent striatal contributions to clinical symptoms, as various conditions including Parkinson’s disease and psychiatric disorders are accompanied by striatal dysfunction [52, 53].”
From Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status (2024) · cites this paper as [52]
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“…pattern of reduced striatal intracellular integrity (caudate RI) with cognitive impairment, which may point to AD-independent striatal contributions to clinical symptoms, as various conditions including Parkinson’s disease and psychiatric disorders are accompanied by striatal dysfunction [52, 53].”
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Dopamine lesions alter the striatal encoding of single-limb gaitPreprint
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The Basal Ganglia and Mesencephalic Locomotor Region Connectivity Matrix
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- Authors
- Zhai, S., Shen, W., Graves, S. M., & Surmeier, D. J.
- Affiliations
- Northwestern University (US)
- University of Minnesota (US)
- Corresponding author
- Surmeier, D. James
- Venue
- Journal of Neural Transmission
- Published
- 2019-04
- Volume
- 126
- Issue
- 4
- Pages
- 411-422
- ISSN
- 0300-9564 (ISSN-L)
- 1435-1463
- PMC
- PMC6544905
- OpenAlex
- W2934839137
- Cited by
- 100
- References
- 130
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 14 · 2023: 16 · 2022: 20 · 2021: 18 · 2020: 10 · 2019: 3 · 2012: 1
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neural Transmission (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- JPB Foundation
- IDP Foundation
- USPHS
- Bumpus Foundation
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- Parkinson's disease, striatum, dopaminergic modulation, levodopa-induced dyskinesia, medium spiny neurons, striatal interneurons, synaptic plasticity, direct and indirect pathways, neuronal ensembles, dopamine receptors, goal-directed behavior, homeostatic adaptation
- MeSH terms
- Animals, Corpus Striatum, Dopamine, Dyskinesia, Drug-Induced, Humans, Levodopa, Parkinson Disease, Dopaminergic Neurons
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