{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Palmer D"],"funding":["National Institute of Neurological Disorders and Stroke","NINDS NIH HHS"],"pagination":["966-978"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12927675"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["67(2)"],"pubmed_abstract":["<h4>Objective</h4>For over four decades, the substantia nigra pars reticulata (SNr) has been recognized as a critical structure in the modulation of seizure activity. Pharmacological and optogenetic inhibition of the SNr produces robust seizure suppression in a range of seizure models. These findings have given rise to a longstanding, yet unresolved question: do seizures involve a failure of inhibition within the SNr?<h4>Methods</h4>We recorded single-unit activity in the SNr during spike-and-wave discharges (SWDs) in male and female WAG/Rij rats, a model of genetic absence epilepsy. We monitored extracellular γ-aminobutyric acid (GABA) levels using intensity-based GABA sensing fluorescence reporter (iGABASnFR). To emphasize the multi-modal efficacy of SNr inhibition on seizure suppression, we optogenetically inhibited the SNr.<h4>Results</h4>Fifty percent of recorded neurons exhibited a marked increase in firing at SWD onset, with activity returning to baseline at SWD termination. Extracellular GABA levels revealed a decrease in fluorescence during SWDs, consistent with reduced GABAergic transmission. Optogenetic inhibition of SNr neurons using continuous (open-loop) inhibition, but not closed-loop (responsive) inhibition, significantly reduced SWD incidence.<h4>Significance</h4>These data suggest that a loss of GABAergic input to the SNr is associated with increased neuronal activity. Optogenetically restoring inhibition effectively reduced seizure burden. Together, these findings address a long-standing gap in the literature and provide compelling evidence that impaired inhibition within the SNr contributes to seizure expression."],"journal":["Epilepsia"],"pubmed_title":["Restoring failed inhibition in the substantia nigra pars reticulata suppresses absence seizures in rats."],"pmcid":["PMC12927675"],"funding_grant_id":["T32NS041218","R01NS097762"],"pubmed_authors":["Forcelli PA","Palmer D"],"additional_accession":[]},"is_claimable":false,"name":"Restoring failed inhibition in the substantia nigra pars reticulata suppresses absence seizures in rats.","description":"<h4>Objective</h4>For over four decades, the substantia nigra pars reticulata (SNr) has been recognized as a critical structure in the modulation of seizure activity. Pharmacological and optogenetic inhibition of the SNr produces robust seizure suppression in a range of seizure models. These findings have given rise to a longstanding, yet unresolved question: do seizures involve a failure of inhibition within the SNr?<h4>Methods</h4>We recorded single-unit activity in the SNr during spike-and-wave discharges (SWDs) in male and female WAG/Rij rats, a model of genetic absence epilepsy. We monitored extracellular γ-aminobutyric acid (GABA) levels using intensity-based GABA sensing fluorescence reporter (iGABASnFR). To emphasize the multi-modal efficacy of SNr inhibition on seizure suppression, we optogenetically inhibited the SNr.<h4>Results</h4>Fifty percent of recorded neurons exhibited a marked increase in firing at SWD onset, with activity returning to baseline at SWD termination. Extracellular GABA levels revealed a decrease in fluorescence during SWDs, consistent with reduced GABAergic transmission. Optogenetic inhibition of SNr neurons using continuous (open-loop) inhibition, but not closed-loop (responsive) inhibition, significantly reduced SWD incidence.<h4>Significance</h4>These data suggest that a loss of GABAergic input to the SNr is associated with increased neuronal activity. Optogenetically restoring inhibition effectively reduced seizure burden. Together, these findings address a long-standing gap in the literature and provide compelling evidence that impaired inhibition within the SNr contributes to seizure expression.","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Feb","modification":"2026-07-16T18:28:55.513Z","creation":"2026-07-09T11:14:58.584Z"},"accession":"S-EPMC12927675","cross_references":{"pubmed":["41182510"],"doi":["10.1111/epi.18701"]}}