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G i/o protein‐coupled receptors inhibit neurons but activate astrocytes and stimulate gliotransmission
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Abstract G protein‐coupled receptors (GPCRs) play key roles in intercellular signaling in the brain. Their effects on cellular function have been largely studied in neurons, but their functional consequences on astrocytes are less known. Using both endogenous and chemogenetic approaches with DREADDs, we have investigated the effects of G q and G i/o GPCR activation on astroglial Ca 2+ ‐based activity, gliotransmitter release, and the functional consequences on neuronal electrical activity. We found that while G q GPCR activation led to cellular activation in both neurons and astrocytes, G i/o GPCR activation led to cellular inhibition in neurons and cellular activation in astrocytes. Astroglial activation by either G q or G i/o protein‐mediated signaling stimulated gliotransmitter release, which increased neuronal excitability. Additionally, activation of G q and G i/o DREADDs in vivo increased astrocyte Ca 2+ activity and modified neuronal network electrical activity. Present results reveal additional complexity of the signaling consequences of excitatory and inhibitory neurotransmitters in astroglia‐neuron network operation and brain function.
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“Previous research also showed that activation of astrocytes in the mouse hippocampus using the Gq-DREADD influences the excitability of neurons.”
From Single-cell resolution analysis of the crosstalk between chemogenically activated astrocytes and microglia (2020) · cites this paper as Durkee et al., 2019
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“The increased intracellular Ca 2+ levels stimulated glutamate release which resulted in activation of neuronal NMDA receptors (Durkee et al., 2019).”
From Single-cell resolution analysis of the crosstalk between chemogenically activated astrocytes and microglia (2020) · cites this paper as Durkee et al., 2019
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Self-citation
Metadata
- Authors
- Durkee, C. A., Covelo, A., Lines, J., Kofuji, P., Aguilar, J., & Araque, A.
- Affiliations
- University of Minnesota (US)
- Hospital Nacional de Parapléjicos (ES)
- Corresponding author
- Araque, Alfonso
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2019-02-23
- Volume
- 67
- Issue
- 6
- Pages
- 1076-1093
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- PMC
- PMC6462242
- OpenAlex
- W2915270937
- Cited by
- 224
- References
- 89
- Citations by year
- 2026: 23 · 2025: 36 · 2024: 31 · 2023: 33 · 2022: 32 · 2021: 35 · 2020: 24 · 2019: 10
- FWCI
- 12.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RUIdeRA - Institutional University Repository (University of Castilla-La Mancha) (submittedVersion)
- Funders
- National Institutes of Health (R01NS097312, R01NS108686, F31AG057155‐01A1, F31NS093751)
- Human Frontier Science Program (RGP0036/2014)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- G protein-coupled receptors, astrocytes, neurons, gliotransmission, gliotransmitter release, neuronal excitability, neuronal network activity, chemogenetic activation, DREADD, astrocyte-neuron communication
- MeSH terms
- Animals, Astrocytes, Female, Hippocampus, Male, Mice, Inbred C57BL, Mice, Transgenic, Neural Inhibition, Neuroglia, Neurons, Organ Culture Techniques, Muscarinic Antagonists, GTP-Binding Protein alpha Subunits, Gi-Go, Receptors, G-Protein-Coupled, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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