{"doi":"10.1016/j.brs.2025.103017","title":"Trigeminal nerve direct current stimulation modulates raphe–hippocampal network synchrony in rats","abstract":"Background Trigeminal nerve stimulation is a promising noninvasive method to modulate subcortical circuits involved in cognition. This study investigated the influence of trigeminal nerve direct current stimulation (TN-DCS) on neuronal activity and coherence between the raphe nuclei and hippocampus. Methods Fourteen adult male Sprague-Dawley rats (n = 10 control; n=4 xylocaine/agonist) were implanted with silicon probes for simultaneous recordings from the hippocampus and either the dorsal (DRN) or median raphe nucleus (MnRN). Direct currents (from ±0.25 to ±3 mA) were applied to the trigeminal nerve during 3-minute sessions (1 minute pre-, 1 minute during, 1 minute post-stimulation). Results Acute TN-DCS rapidly and reversibly modulated firing in the DRN, MnRN, and hippocampus in a cell–type–specific, amplitude-dependent manner. Putative non-serotonergic (p-non-SERT) raphe neurons exhibited strong increases in spike rate, whereas putative serotonergic (p-SERT) neurons did not show consistent rate changes or stimulation-induced bursts. In the hippocampus, pyramidal cells exhibited polarity-dependent, amplitude-scaled increases in spike rate, whereas interneurons displayed smaller effects that were independent of polarity. TN-DCS enhanced theta-band coupling between p-non-SERT raphe spikes and hippocampal local field potentials, increasing spike-field coherence and spike-triggered averages in both DRN and MnRN. These effects, along with spike-rate increases in MnRN and hippocampus caused by TN-DCS, were blocked or significantly reduced by local trigeminal block (xylocaine) or intra-MnRN 5-HT 1A/7 agonist (8-OH-DPAT). Conclusions TN-DCS dynamically modulates raphe–hippocampal firing and theta synchrony via predominantly amplitude-dependent mechanisms that require intact trigeminal input and serotonergic signaling, supporting its potential as a targeted neuromodulation approach for subcortical circuits involved in cognition and mood.","journal":"Brain stimulation","year":2025,"id":587523,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1226427,"name":"Liyi Chen","orcid":"0000-0002-3288-1741","position":1,"is_corresponding":false},{"id":696389,"name":"Myles Mc Laughlin","orcid":"0000-0001-8574-1841","position":2,"is_corresponding":false},{"id":1166189,"name":"Alireza Majdi","orcid":"0000-0002-2990-4762","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T02:59:39.958043Z","pmid":"41482154","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":[]}