{"doi":"10.64898/2025.12.19.695581","title":"Characterization and application of hyperthermia-evoked seizures in a mouse model of focal cortical dysplasia","abstract":"Abstract Rodent models of drug-resistant epilepsy are widely used to uncover mechanisms of seizures and to test the efficacy of treatments; however, the stochastic and relatively infrequent nature of spontaneous seizures in these models makes it challenging to observe and manipulate peri-ictal activity, and to rapidly screen therapeutics. As fever has been identified as a clinical seizure trigger, we investigated the ability of induced hyperthermia to trigger seizures in a mouse model of focal cortical dysplasia (FCD), a common cause of drug-resistant epilepsy. Experimental mice were generated via in utero electroporation of a gain-of-function RHEB variant (RHEBp.P37L). In adult Rheb- FCD mice, hyperthermia elicited behavioral seizures ∼80% of the time, with a mean temperature threshold of ∼40 °C. Using this acute paradigm, as a proof-of-concept, we found that chemogenetic inhibition of a subset of excitatory neurons within the dysplasia significantly elevated the threshold for hyperthermia-evoked seizures. We then confirmed the relevance of this acute finding to spontaneous epileptiform activity, using repeated chemogenetic inhibition across chronic recordings to confirm a reduction of spontaneous seizures as well as interictal spikes. Overall, our data demonstrate that hyperthermia-evoked seizures can be readily elicited in Rheb- FCD mice, offering a tractable platform for evaluating therapeutic interventions targeting seizure susceptibility in focal epilepsy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":586845,"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":0.9577,"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":1324627,"name":"Chandni Rana","orcid":"0009-0000-2269-112X","position":1,"is_corresponding":false},{"id":1501932,"name":"Ruitao Shen","orcid":null,"position":2,"is_corresponding":false},{"id":298821,"name":"Tao Yang","orcid":"0000-0002-4182-9793","position":3,"is_corresponding":false},{"id":960021,"name":"Joseph Barden","orcid":null,"position":4,"is_corresponding":false},{"id":1501933,"name":"Hudson Haberland","orcid":null,"position":5,"is_corresponding":false},{"id":1386215,"name":"Mi Jiang","orcid":null,"position":6,"is_corresponding":false},{"id":1501934,"name":"Rida Qureshi","orcid":null,"position":7,"is_corresponding":false},{"id":1501935,"name":"Saif Siddiqui","orcid":null,"position":8,"is_corresponding":false},{"id":1501936,"name":"Alexander Sajdak","orcid":null,"position":9,"is_corresponding":false},{"id":1501290,"name":"Patrick N. Lawlor","orcid":"0000-0001-7621-3254","position":10,"is_corresponding":false},{"id":916563,"name":"Yan Wang","orcid":"0000-0003-2057-0097","position":11,"is_corresponding":false},{"id":603184,"name":"Joanna Mattis","orcid":"0000-0003-0341-1270","position":12,"is_corresponding":false},{"id":908172,"name":"Xiaogang Zhang","orcid":"0009-0002-6634-9267","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:59:32.191237Z","pmid":"41509259","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":[]}