Data from: Restoring failed inhibition in the substantia nigra pars reticulata suppresses absence seizures in rats

Objective 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
produce 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? Methods 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 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. Results 50% 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. Significance 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.