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Dopamine-Evoked Synaptic Regulation in the Nucleus Accumbens Requires Astrocyte Activity
Open accessAbstract
Dopamine is involved in physiological processes like learning and memory, motor control and reward, and pathological conditions such as Parkinson's disease and addiction. In contrast to the extensive studies on neurons, astrocyte involvement in dopaminergic signaling remains largely unknown. Using transgenic mice, optogenetics, and pharmacogenetics, we studied the role of astrocytes on the dopaminergic system. We show that in freely behaving mice, astrocytes in the nucleus accumbens (NAc), a key reward center in the brain, respond with Ca 2+ elevations to synaptically released dopamine, a phenomenon enhanced by amphetamine. In brain slices, synaptically released dopamine increases astrocyte Ca 2+, stimulates ATP/adenosine release, and depresses excitatory synaptic transmission through activation of presynaptic A 1 receptors. Amphetamine depresses neurotransmission through stimulation of astrocytes and the consequent A 1 receptor activation. Furthermore, astrocytes modulate the acute behavioral psychomotor effects of amphetamine. Therefore, astrocytes mediate the dopamine- and amphetamine-induced synaptic regulation, revealing a novel cellular pathway in the brain reward system.
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“DA signaling is considered to play a key role in astrocyte-neuron crosstalk in the striatum. 79”
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Self-citation
Metadata
- Authors
- Corkrum, M., Covelo, A., Lines, J., Bellocchio, L., Pisansky, M., Loke, K., Quintana, R., Rothwell, P. E., Lujan, R., Marsicano, G., Martin, E. D., Thomas, M. J., Kofuji, P., & Araque, A.
- Affiliations
- University of Minnesota (US)
- Université de Bordeaux (FR)
- Corresponding author
- Araque, Alfonso
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 105
- Issue
- 6
- Pages
- 1036-1047.e5
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC7322729
- OpenAlex
- W2999291880
- Cited by
- 327
- References
- 67
- Citations by year
- 2026: 27 · 2025: 63 · 2024: 62 · 2023: 52 · 2022: 54 · 2021: 48 · 2020: 21
- FWCI
- 20.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 382 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- RUIdeRA - Institutional University Repository (University of Castilla-La Mancha) (submittedVersion, other-oa)
- Funders
- University of Minnesota
- European Research Council (ERC-2017-AdG-786467, RGP0036/2014)
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Human Frontier Science Program
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Keywords
- astrocytes, dopamine, nucleus accumbens, synaptic regulation, astrocyte calcium signaling, adenosine A1 receptor, amphetamine, psychomotor effects, reward systems, dopaminergic signaling
- MeSH terms
- Adenosine, Adenosine Triphosphate, Amphetamine, Animals, Astrocytes, Calcium, Clozapine, Dopamine, Female, Male, Mice, Transgenic, Motor Activity, Synaptic Transmission, Nucleus Accumbens, Reward, Receptors, Dopamine D1, Mice, Knockout, Excitatory Postsynaptic Potentials, Mice, Optogenetics
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