{"doi":"10.1093/brain/awac037","title":"AMPK-mediated potentiation of GABAergic signalling drives hypoglycaemia-provoked spike-wave seizures","abstract":"Metabolism regulates neuronal activity and modulates the occurrence of epileptic seizures. Here, using two rodent models of absence epilepsy, we show that hypoglycaemia increases the occurrence of spike-wave seizures. We then show that selectively disrupting glycolysis in the thalamus, a structure implicated in absence epilepsy, is sufficient to increase spike-wave seizures. We propose that activation of thalamic AMP-activated protein kinase, a sensor of cellular energetic stress and potentiator of metabotropic GABAB-receptor function, is a significant driver of hypoglycaemia-induced spike-wave seizures. We show that AMP-activated protein kinase augments postsynaptic GABAB-receptor-mediated currents in thalamocortical neurons and strengthens epileptiform network activity evoked in thalamic brain slices. Selective thalamic AMP-activated protein kinase activation also increases spike-wave seizures. Finally, systemic administration of metformin, an AMP-activated protein kinase agonist and common diabetes treatment, profoundly increased spike-wave seizures. These results advance the decades-old observation that glucose metabolism regulates thalamocortical circuit excitability by demonstrating that AMP-activated protein kinase and GABAB-receptor cooperativity is sufficient to provoke spike-wave seizures.","journal":"Brain","year":2022,"id":258342,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":406651,"name":"Matthew L Ritger","orcid":"0000-0002-6741-262X","position":1,"is_corresponding":false},{"id":375812,"name":"Pasha A. Davoudian","orcid":"0000-0002-5096-7610","position":2,"is_corresponding":false},{"id":909927,"name":"Finnegan O’Dell","orcid":null,"position":3,"is_corresponding":false},{"id":909928,"name":"Daniel R. Wyskiel","orcid":null,"position":4,"is_corresponding":false},{"id":459751,"name":"George M. P. R. Souza","orcid":"0000-0003-4678-6910","position":5,"is_corresponding":false},{"id":323065,"name":"Adam C Lu","orcid":"0000-0002-1008-1057","position":6,"is_corresponding":false},{"id":832050,"name":"Edward Perez‐Reyes","orcid":"0000-0001-6237-3863","position":7,"is_corresponding":false},{"id":343892,"name":"Joshua C. Drake","orcid":"0000-0001-6658-4975","position":8,"is_corresponding":false},{"id":53359,"name":"Zhen Yan","orcid":"0000-0002-3519-9596","position":9,"is_corresponding":false},{"id":323068,"name":"Mark P. Beenhakker","orcid":"0000-0002-4541-0201","position":10,"is_corresponding":false},{"id":651033,"name":"Kathryn A. Salvati","orcid":"0000-0002-9557-9259","position":0,"is_corresponding":true}],"reference_count":117,"raw_metadata":null,"created_at":"2026-07-19T00:25:38.634785Z","pmid":"35134125","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":[]}