{"doi":"10.1101/2024.02.12.579861","title":"Chemogenetic activation of microglial Gi signaling decreases microglial surveillance and impairs neuronal synchronization","abstract":"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 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":486671,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":660361,"name":"Lingxiao Wang","orcid":"0000-0001-5819-4563","position":1,"is_corresponding":false},{"id":991136,"name":"Yue Liang","orcid":"0000-0002-5925-6743","position":2,"is_corresponding":false},{"id":255100,"name":"Jiaying Zheng","orcid":"0000-0002-7457-6198","position":3,"is_corresponding":false},{"id":559377,"name":"Anthony D. Umpierre","orcid":"0000-0002-1470-8881","position":4,"is_corresponding":false},{"id":258025,"name":"Long‐Jun Wu","orcid":"0000-0001-8019-3380","position":5,"is_corresponding":false},{"id":689266,"name":"Shunyi Zhao","orcid":"0000-0001-7265-0801","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T02:08:01.404471Z","pmid":"38405754","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}