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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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Novel anticancer drugs related to cardiotoxicity
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Stimulation Paradigms and Transduction Patterns for Optogenetic Intervention of Astrocytes
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Neuronal-Glial Interactions in Learning and Behavior under Normal Conditions and during Oncogenesis
Venerina, Y. A., Venerin, A. А., Gorkin, A. G., & Alexandrov, Y. I. (2025) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-025-01867-z · Cited by 2
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
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