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Dopamine D2 Receptors Regulate the Anatomical and Functional Balance of Basal Ganglia Circuitry
Open accessAbstract
Structural plasticity in the adult brain is essential for adaptive behavior. We have found a remarkable anatomical plasticity in the basal ganglia of adult mice that is regulated by dopamine D2 receptors (D2Rs). By modulating neuronal excitability, striatal D2Rs bidirectionally control the density of direct pathway collaterals in the globus pallidus that bridge the direct pathway with the functionally opposing indirect pathway. An increase in bridging collaterals is associated with enhanced inhibition of pallidal neurons in vivo and disrupted locomotor activation after optogenetic stimulation of the direct pathway. Chronic blockade with haloperidol, an antipsychotic medication used to treat schizophrenia, decreases the extent of bridging collaterals and rescues the locomotor imbalance. These findings identify a role for bridging collaterals in regulating the concerted balance of striatal output and may have important implications for understanding schizophrenia, a disease involving excessive activation of striatal D2Rs that is treated with D2R blockers.
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“b) bridging collaterals between direct and indirect pathways may permit modulation of information transmission through CSTC circuits 49.”
From DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS: Review: Dissecting OCD Circuits: Animals to Treatments (2015) · cites this paper as [49]
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Metadata
- Authors
- Cazorla, M., de Carvalho, F. D., Chohan, M. O., Shegda, M., Chuhma, N., Rayport, S., Ahmari, S. E., Moore, H., & Kellendonk, C.
- Affiliations
- New York State Psychiatric Institute (US)
- University of Pittsburgh (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Kellendonk, Christoph
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 81
- Issue
- 1
- Pages
- 153-164
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3899717
- OpenAlex
- W1993833941
- Cited by
- 226
- References
- 43
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 8 · 2023: 24 · 2022: 9 · 2021: 22 · 2020: 22 · 2019: 28 · 2018: 22 · 2017: 18 · 2016: 35 · 2015: 15 · 2014: 8
- FWCI
- 11.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- National Institute of Mental Health (P50MH086404, R01MH093672, K08MH087718)
- National Institute on Drug Abuse (R01DA038966)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Keywords
- dopamine D2 receptor, basal ganglia, anatomical plasticity, direct pathway, indirect pathway, globus pallidus, striatal output, neuronal excitability, locomotor behavior, haloperidol, schizophrenia, antipsychotic drugs, dopamine D2 receptor antagonists
- MeSH terms
- Action Potentials, Animals, Basal Ganglia, Corpus Striatum, Doxycycline, Gene Expression Regulation, Globus Pallidus, Haloperidol, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Nerve Net, Neural Pathways, Neurons, Time Factors, Receptors, Dopamine D1, Receptors, Dopamine D2, Dopamine Antagonists, Potassium Channels, Inwardly Rectifying, Green Fluorescent Proteins, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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