Cited by 224Neuroscience and Neuropharmacology ResearchReceptor Mechanisms and SignalingNeuroinflammation and Neurodegeneration Mechanisms

G i/o protein‐coupled receptors inhibit neurons but activate astrocytes and stimulate gliotransmission

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Durkee, Caitlin A., Covelo, Ana, Lines, Justin, Kofuji, Paulo, Aguilar, Juan, Araque, Alfonso·2019·Glia

Abstract

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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  1. Araque A, Martin ED, Perea G, Arellano JI, & Buno W (2002). Synaptically released acetylcholine evokes Ca2+ elevations in astrocytes in hippocampal slices. J Neurosci, 22(7), 2443– 2450. doi: 20026212 11923408 PMC6758296

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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
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
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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