Modulation of in vitro Network Activity by Optogenetic Stimulation of Parvalbumin-positive Interneurons During Estrous Cycle

Background: Catamenial epilepsy, which is defined as a periodicity of seizure exacerbation occurring during the menstrual cycle, has been reported in up to 70% of epileptic women. These seizures are often non-responsive to medication and our understanding of the relation between menstrual cycle and seizure generation (i.e. ictogenesis) remains limited. Methods: Here, we employed the in vitro 4-aminopyridine model of epileptiform synchronization, to analyze the effects induced by optogenetic activation of parvalbumin (PV)-positive interneurons at 8 Hz during estrous and non-estrous phases in female PV-ChR2 mice. Results: We found that: (i) optogenetic stimulation of PV-positive interneurons induced an initial interictal spike followed by field oscillations occurring more often in estrous (59%) than in non-estrous slices (17%); (ii) these oscillations showed significantly higher power in estrous compared to nonestrous slices (p < 0.001); (iii) significantly higher rates of interictal spikes and ictal discharges were identified in both estrous and non-estrous slices during optogenetic stimulation of PV-positive interneurons compared to periods of no stimulation (p < 0.05); and (iv) ictal events appeared to occur more frequently during optogenetic stimulation in estrous compared to non-estrous slices. Conclusion: Our findings show that optogenetic activation of PV-interneurons leads to more powerful network oscillations and more frequent ictal discharges in estrous than in non-estrous slices. We conclude that during the rodent estrous cycle, PV-interneuron hyperexcitability may play a role in epileptiform synchronization and thus in catamenial seizures.