Chemogenetic activation of microglial Gi signaling decreases microglial surveillance and impairs neuronal synchronization
Microglia actively survey the brain and dynamically interact with neurons to maintain brain homeostasis. Microglial Gi-protein coupled receptors (Gi-GPCRs) play a critical role in microglia-neuron communications. However, the impact of temporally activating microglial Gi signaling on microglial dynamics and neuronal activity in the homeostatic brain remains largely unknown. In this study, we employed Gi-based Designer Receptors Exclusively Activated by Designer Drugs (Gi-DREADD) to selectively and temporally modulate microglial Gi signaling pathway. By integrating this chemogenetic approach with in vivo two-photon imaging, we observed that exogenous activation of microglial Gi signaling transiently inhibited microglial process dynamics, reduced neuronal activity, and impaired neuronal synchronization. These altered neuronal functions were associated with a decrease in interactions between microglia and neuron somata. Altogether, this study demonstrates that acute, exogenous activation of microglial Gi signaling can regulate neuronal circuit function, offering a potential pharmacological target for neuromodulation through microglia.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2024 |
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Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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Enthalten in: |
bioRxiv : the preprint server for biology - (2024) vom: 12. Feb. |
Sprache: |
Englisch |
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Beteiligte Personen: |
Zhao, Shunyi [VerfasserIn] |
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Anmerkungen: |
Date Revised 26.02.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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doi: |
10.1101/2024.02.12.579861 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM368957276 |
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520 | |a Microglia actively survey the brain and dynamically interact with neurons to maintain brain homeostasis. Microglial Gi-protein coupled receptors (Gi-GPCRs) play a critical role in microglia-neuron communications. However, the impact of temporally activating microglial Gi signaling on microglial dynamics and neuronal activity in the homeostatic brain remains largely unknown. In this study, we employed Gi-based Designer Receptors Exclusively Activated by Designer Drugs (Gi-DREADD) to selectively and temporally modulate microglial Gi signaling pathway. By integrating this chemogenetic approach with in vivo two-photon imaging, we observed that exogenous activation of microglial Gi signaling transiently inhibited microglial process dynamics, reduced neuronal activity, and impaired neuronal synchronization. These altered neuronal functions were associated with a decrease in interactions between microglia and neuron somata. Altogether, this study demonstrates that acute, exogenous activation of microglial Gi signaling can regulate neuronal circuit function, offering a potential pharmacological target for neuromodulation through microglia | ||
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700 | 1 | |a Liang, Yue |e verfasserin |4 aut | |
700 | 1 | |a Zheng, Jiaying |e verfasserin |4 aut | |
700 | 1 | |a Umpierre, Anthony D |e verfasserin |4 aut | |
700 | 1 | |a Wu, Long-Jun |e verfasserin |4 aut | |
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