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Cited by 735Cannabis and Cannabinoid ResearchParkinson's Disease Mechanisms and TreatmentsNeuroscience and Neuropharmacology Research

The DOI matches its Crossref record; 34 of the 35 references it cites were found in a registry or an index.

Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson's disease models

Kreitzer, Anatol C., Malenka, Robert C.·2007·Nature
DOI 10.1038/nature05506
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Abstract

The striatum is a major forebrain nucleus that integrates cortical and thalamic afferents and forms the input nucleus of the basal ganglia. Striatal projection neurons target the substantia nigra pars reticulata (direct pathway) or the lateral globus pallidus (indirect pathway). Imbalances between neural activity in these two pathways have been proposed to underlie the profound motor deficits observed in Parkinson's disease and Huntington's disease. However, little is known about differences in cellular and synaptic properties in these circuits. Indeed, current hypotheses suggest that these cells express similar forms of synaptic plasticity. Here we show that excitatory synapses onto indirect-pathway medium spiny neurons (MSNs) exhibit higher release probability and larger N-methyl-d-aspartate receptor currents than direct-pathway synapses. Moreover, indirect-pathway MSNs selectively express endocannabinoid-mediated long-term depression (eCB-LTD), which requires dopamine D2 receptor activation. In models of Parkinson's disease, indirect-pathway eCB-LTD is absent but is rescued by a D2 receptor agonist or inhibitors of endocannabinoid degradation. Administration of these drugs together in vivo reduces parkinsonian motor deficits, suggesting that endocannabinoid-mediated depression of indirect-pathway synapses has a critical role in the control of movement. These findings have implications for understanding the normal functions of the basal ganglia, and also suggest approaches for the development of therapeutic drugs for the treatment of striatal-based brain disorders.

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Metadata

Authors
Kreitzer, A. C., & Malenka, R. C.
Affiliations
Stanford Medicine (US)
Corresponding author
Malenka, Robert C.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2007-02
Volume
445
Issue
7128
Pages
643-647
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature05506
OpenAlex
W2003314029
Cited by
735
References
35
Citations by year
2026: 12 · 2025: 21 · 2024: 21 · 2023: 17 · 2022: 17 · 2021: 34 · 2020: 28 · 2019: 41 · 2018: 41 · 2017: 45 · 2016: 37 · 2015: 34 · 2014: 37 · 2013: 31 · 2012: 47
FWCI
44.31
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
striatum, indirect pathway, direct pathway, medium spiny neurons, dopamine D2 receptor, basal ganglia, motor impairment, synaptic plasticity, NMDA receptor currents, release probability, transgenic mouse model, therapeutic target, Huntington's disease, substantia nigra pars reticulata
MeSH terms
Animals, Benzamides, Carbamates, Disease Models, Animal, Dopamine, Mice, Transgenic, Morpholines, Naphthalenes, Neuronal Plasticity, Parkinson Disease, Piperidines, Psychomotor Performance, Pyrazoles, Reserpine, Synapses, Receptors, N-Methyl-D-Aspartate, Oxidopamine, Neostriatum, Receptors, Dopamine D2, Excitatory Postsynaptic Potentials, Long-Term Synaptic Depression, Receptor, Cannabinoid, CB1, Benzoxazines, Mice, Cannabinoid Receptor Modulators, Endocannabinoids, Dopamine D2 Receptor Antagonists, In Vitro Techniques

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