Gi/o protein-coupled receptors inhibit neurons but activate astrocytes and stimulate gliotransmission
Gi/o protein-coupled receptors inhibit neurons but activate astrocytes and stimulate gliotransmission
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DOI：
10.1002/glia.23589
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发表时间：
2019-06-01
期刊：
影响因子：
6.2
通讯作者：
Araque, Alfonso
中科院分区：
文献类型：
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作者：
Durkee, Caitlin A.;Covelo, Ana;Araque, Alfonso
G蛋白偶联受体（gpcr）在大脑细胞间信号传导中起着关键作用。它们对神经元细胞功能的影响已被大量研究，但它们对星形胶质细胞的功能影响尚不清楚。利用内源性和化学发生的方法，我们研究了G(q)和G(i/o) GPCR激活对星形胶质细胞Ca2+活性、胶质递质释放的影响，以及对神经元电活动的功能影响。我们发现G(q)GPCR激活导致神经元和星形胶质细胞的细胞激活，而G(i/o)GPCR激活导致神经元的细胞抑制和星形胶质细胞的细胞激活。G(q)或G（i/o）蛋白介导的信号激活星形胶质细胞，刺激胶质递质释放，从而增加神经元的兴奋性。此外，体内G(q)和G(i/o) DREADDs的激活增加了星形胶质细胞Ca2+活性，并改变了神经元网络电活动。目前的研究结果揭示了星形胶质神经元网络运作和脑功能中兴奋性和抑制性神经递质信号传导后果的额外复杂性。
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 Ca2+-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 Ca2+ 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.