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Microglia, the resident macrophages in the central nervous system, express receptors for classical neurotransmitters, such as γ-aminobutyric acid (GABA) and glutamate, suggesting that they sense synaptic activity. To detect microglial Ca2+ responses to neuronal activity, we generate transgenic mouse lines expressing the fluorescent Ca2+ indicator GCaMP6m, specifically in microglia and demonstrate that electrical stimulation of the Schaffer collateral pathway results in microglial Ca2+ responses in early postnatal but not adult hippocampus. Preceding the microglial responses, we also observe similar Ca2+ responses in astrocytes, and both are sensitive to tetrodotoxin. Blocking astrocytic glutamate uptake or GABA transport abolishes stimulation-induced microglial responses as well as antagonizing the microglial GABAB receptor. Our data, therefore, suggest that the neuronal activity-induced glutamate uptake and the release of GABA by astrocytes trigger the activation of GABAB receptors in microglia. This neuron, astrocyte, and microglia communication pathway might modulate microglial activity in developing neuronal networks. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Francesca Logiacco, Pengfei Xia, Svilen Veselinov Georgiev, Celeste Franconi, Yi-Jen Chang, Bilge Ugursu, Anje Sporbert, Ralf Kühn, Helmut Kettenmann, Marcus Semtner. Microglia sense neuronal activity via GABA in the early postnatal hippocampus. Cell reports. 2021 Dec 28;37(13):110128

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PMID: 34965412

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