Cortical regulation of dopamine depletion-induced dendritic spine loss in striatal medium spiny neurons
Open accessAbstract
The proximate cause of Parkinson's disease is striatal dopamine depletion. Although no overt toxicity to striatal neurons has been reported in Parkinson's disease, one of the consequences of striatal dopamine loss is a decrease in the number of dendritic spines on striatal medium spiny neurons (MSNs). Dendrites of these neurons receive cortical glutamatergic inputs onto the dendritic spine head and dopaminergic inputs from the substantia nigra onto the spine neck. This synaptic arrangement suggests that dopamine gates corticostriatal glutamatergic drive onto spines. Using triple organotypic slice cultures composed of ventral mesencephalon, striatum, and cortex of the neonatal rat, we examined the role of the cortex in dopamine depletion-induced dendritic spine loss in MSNs. The striatal dopamine innervation was lesioned by treatment of the cultures with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+) or by removing the mesencephalon. Both MPP+ and mesencephalic ablation decreased MSN dendritic spine density. Analysis of spine morphology revealed that thin spines were preferentially lost after dopamine depletion. Removal of the cortex completely prevented dopamine depletion-induced spine loss. These data indicate that the dendritic remodeling of MSNs seen in parkinsonism occurs secondary to increases in corticostriatal glutamatergic drive, and suggest that modulation of cortical activity may be a useful therapeutic strategy in Parkinson's disease.
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- Authors
- Neely, M. D., Schmidt, D. E., & Deutch, A. Y.
- Affiliations
- Vanderbilt Psychiatric Hospital (US)
- ORCID
- Neely, M.D.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 149
- Issue
- 2
- Pages
- 457-464
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC2094700
- OpenAlex
- W2048760615
- Cited by
- 80
- References
- 64
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 5 · 2014: 1 · 2013: 7 · 2012: 8
- FWCI
- 6.68
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5p01ns044282-05)
- National Institute of Mental Health (R01MH077298)
- National Institute of Neurological Disorders and Stroke (P01-NS044282)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- Parkinson's disease, striatal dopamine depletion, dendritic spine loss, striatal medium spiny neurons, MPP+, dendritic spine morphology, dendritic remodeling, organotypic slice cultures, substantia nigra
- MeSH terms
- Animals, Cerebral Cortex, Chromatography, High Pressure Liquid, Denervation, Dopamine, Coloring Agents, Homovanillic Acid, Immunohistochemistry, Mesencephalon, Neurons, Neurons, Afferent, Organ Culture Techniques, Propidium, Tyrosine 3-Monooxygenase, Neostriatum, Rats, Sprague-Dawley, Coculture Techniques, Dendritic Spines, Rats
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