Chemogenetic activation of microglial Gi signaling decreases microglial surveillance and impairs neuronal synchronization
Abstract 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 within vivotwo-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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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 15. Feb. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhao, Shunyi [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2024.02.12.579861 |
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| PPN (Katalog-ID): |
XBI042483204 |
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| 245 | 1 | 0 | |a Chemogenetic activation of microglial Gi signaling decreases microglial surveillance and impairs neuronal synchronization |
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| 520 | |a Abstract 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 within vivotwo-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. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
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| 700 | 1 | |a Wang, Lingxiao |4 aut | |
| 700 | 1 | |a Liang, Yue |4 aut | |
| 700 | 1 | |a Zheng, Jiaying |4 aut | |
| 700 | 1 | |a Umpierre, Anthony D. |4 aut | |
| 700 | 1 | |a Wu, Long-Jun |0 (orcid)0000-0001-8019-3380 |4 aut | |
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