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Publication : G<sub>i/o</sub> protein-coupled receptors inhibit neurons but activate astrocytes and stimulate gliotransmission.

First Author  Durkee CA Year  2019
Journal  Glia Volume  67
Issue  6 Pages  1076-1093
PubMed ID  30801845 Mgi Jnum  J:274727
Mgi Id  MGI:6287536 Doi  10.1002/glia.23589
Citation  Durkee CA, et al. (2019) Gi/o protein-coupled receptors inhibit neurons but activate astrocytes and stimulate gliotransmission. Glia 67(6):1076-1093
abstractText  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 Gq and Gi/o GPCR activation on astroglial Ca(2+) -based activity, gliotransmitter release, and the functional consequences on neuronal electrical activity. We found that while Gq GPCR activation led to cellular activation in both neurons and astrocytes, Gi/o GPCR activation led to cellular inhibition in neurons and cellular activation in astrocytes. Astroglial activation by either Gq or Gi/o protein-mediated signaling stimulated gliotransmitter release, which increased neuronal excitability. Additionally, activation of Gq and Gi/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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