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

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

Research output: Contribution to journalArticle

7 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1076-1093
Number of pages18
Issue number6
StatePublished - Jun 2019



  • G protein-coupled receptors
  • astrocyte Ca
  • astrocytes
  • gliotransmission

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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