{"doi":"10.1101/2021.06.25.449915","title":"PV-specific loss of the transcriptional coactivator PGC-1α slows down the evolution of epileptic activity in an acute ictogenic model","abstract":"Abstract The transcriptional coactivator, PGC-1α (peroxisome proliferator activated receptor gamma coactivator 1α), plays a key role coordinating energy requirement within cells. Its importance is reflected in the growing number of psychiatric and neurological conditions that have been associated with reduced PGC-1α levels. In cortical networks, PGC-1α is required for the induction of parvalbumin (PV) expression in interneurons, and PGC-1α deficiency affects synchronous GABAergic release. It is unknown, however, how this affects cortical excitability. We show here that knocking down PGC-1α specifically in the PV-expressing cells (PGC-1α PV-/- ), blocks the activity-dependent regulation of the synaptic proteins, SYT2 and CPLX1 . More surprisingly, this cell-class specific knock-out of PGC-1α appears to have a novel anti-epileptic effect, as assayed in brain slices bathed in 0 Mg 2+ media. The rate of pre-ictal discharges developed approximately equivalently in wild-type and PGC-1α PV-/- brain slices, but the intensity of these discharges was lower in PGC-1α PV-/- slices, as evident from the reduced power in the gamma range and reduced firing rates in both PV interneurons and pyramidal cells during these discharges. Reflecting this reduced intensity in the pre-ictal discharges, the PGC-1α PV-/- brain slices experienced many more discharges before transitioning into a seizure-like event. Consequently, there was a large increase in the latency to the first seizure-like event in brain slices lacking PGC-1α in PV interneurons. We conclude that knocking down PGC-1α limits the range of PV interneuron firing, and this slows the pathophysiological escalation during ictogenesis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":225405,"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":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":828230,"name":"Connie Mackenzie-Gray-Scott","orcid":null,"position":1,"is_corresponding":false},{"id":792110,"name":"Darren Walsh","orcid":"0000-0002-8010-8067","position":2,"is_corresponding":false},{"id":792111,"name":"Claudia Racca","orcid":"0009-0004-9997-3271","position":3,"is_corresponding":false},{"id":630954,"name":"Rita M. Cowell","orcid":"0000-0001-5814-9412","position":4,"is_corresponding":false},{"id":272176,"name":"Andrew J. Trevelyan","orcid":"0000-0001-9307-4241","position":5,"is_corresponding":false},{"id":792109,"name":"R. Ryley Parrish","orcid":"0000-0001-6798-6140","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-18T23:54:26.581453Z","pmid":null,"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":[]}