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G i/o protein‐coupled receptors inhibit neurons but activate astrocytes and stimulate gliotransmission
Author(s) -
Durkee Caitlin A.,
Covelo Ana,
Lines Justin,
Kofuji Paulo,
Aguilar Juan,
Araque Alfonso
Publication year - 2019
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23589
Subject(s) - g protein coupled receptor , astrocyte , biology , neuroscience , excitatory postsynaptic potential , receptor , premovement neuronal activity , inhibitory postsynaptic potential , g protein , neuron , microbiology and biotechnology , signal transduction , central nervous system , biochemistry
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.