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Review
. 2021 Feb 21:456:71-84.
doi: 10.1016/j.neuroscience.2020.03.025. Epub 2020 Mar 26.

G-Protein-Coupled Receptors in Astrocyte-Neuron Communication

Paulo Kofuji  1 , Alfonso Araque  2
Affiliations
Review

G-Protein-Coupled Receptors in Astrocyte-Neuron Communication

Paulo Kofuji et al. Neuroscience. .

Abstract

Astrocytes, a major type of glial cell, are known to play key supportive roles in brain function, contributing to ion and neurotransmitter homeostasis, maintaining the blood-brain barrier and providing trophic and metabolic support for neurons. Besides these support functions, astrocytes are emerging as important elements in brain physiology through signaling exchange with neurons at tripartite synapses. Astrocytes express a wide variety of neurotransmitter transporters and receptors that allow them to sense and respond to synaptic activity. Principal among them are the G-protein-coupled receptors (GPCRs) in astrocytes because their activation by synaptically released neurotransmitters leads to mobilization of intracellular calcium. In turn, activated astrocytes release neuroactive substances called gliotransmitters, such as glutamate, GABA, and ATP/adenosine that lead to synaptic regulation through activation of neuronal GPCRs. In this review we will present and discuss recent evidence demonstrating the critical roles played by GPCRs in the bidirectional astrocyte-neuron signaling, and their crucial involvement in the astrocyte-mediated regulation of synaptic transmission and plasticity.

Keywords: astrocytes; astrocyte–neuron signaling; gliotransmission; gliotransmitters; synaptic plasticity; tripartite synapses.

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Figures

FIGURE 1:
FIGURE 1:. Neuron-Astrocyte Signaling at the Tripartite Synapse.
Presynaptic neurons release neurotransmitters (1) that bind to GPCR in postsynaptic cells and astrocytes (2). Activation of GPCRs in astrocytes elicits the activation of PLC cascade (5) resulting in elevation of intracellular Ca2+ (6). Increases in postsynaptic Ca2+ also leads to release of ECBs (3) that activate CBIRs (4). mGluR, metabotropic glutamate receptor; CB1R, cannabinoid receptor type 1; P2YR, purinergic receptor type 2; GABABR, GABA receptor type B; D1R; dopamine receptor type 1; AR, adenosine receptor; MOR, p-type opioid receptor; DLGa, diacylglycerol lipase type a; PLC, phospholipase C.
FIGURE 2:
FIGURE 2:. Astrocyte-Neuron Signaling at the Tripartite Synapse.
Activation of PLC cascade and resulting intracellular Ca2+ increases (1) promotes release of gliotransmitters (2) that act upon presynaptic (3) or postsynaptic (4) GPCRs or channels. Presynaptic release (5) or postsynaptic excitability are therefore regulated by astrocytic released gliotransmitters. mGluR, metabotropic glutamate receptor; P2YR, purinergic receptor type 2; A1R, adenosine receptor type 1; A2AR, adenosine receptor type 2A; NMDAR, N-methyl-D-aspartate receptor; P2XR, purinergic receptor type P2X; PLC, phospholipase C.
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