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Volume 23, Issue 7
  • ISSN: 1570-159X
  • E-ISSN: 1875-6190

Abstract

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 (. ictogenesis) remains limited.

Methods

Here, we employed the 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 non-estrous slices ( 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 ( 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.

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2025-01-22
2025-05-18

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References

  1. McEwenB.S. GouldE. OrchinikM. WeilandN.G. WoolleyC.S. Oestrogens and the structural and functional plasticity of neurons: Implications for memory, ageing and neurodegenerative processes.Ciba Found. Symp.1995191526610.1002/9780470514757.ch4 8582205
     [Google Scholar]
  2. ChristianC.A. ReddyD.S. MaguireJ. ForcelliP.A. Sex differences in the epilepsies and associated comorbidities: Implications for use and development of pharmacotherapies.Pharmacol. Rev.202072476780010.1124/pr.119.017392 32817274
     [Google Scholar]
  3. DuncanS. ReadC.L. BrodieM.J. How common is catamenial epilepsy?Epilepsia199334582783110.1111/j.1528‑1157.1993.tb02097.x 8404732
     [Google Scholar]
  4. ReddyD.S. The neuroendocrine basis of sex differences in epilepsy.Pharmacol. Biochem. Behav.20171529710410.1016/j.pbb.2016.07.002 27424276
     [Google Scholar]
  5. ReddyD.S. RogawskiM.A. Neurosteroids — Endogenous regulators of seizure susceptibility and role in the treatment of epilepsy In: Jasper’s Basic Mechanisms of the EpilepsiesNational Center for Biotechnology Information: (US)Bethesda (MD)2012
     [Google Scholar]
  6. Verrotti AlbertoA. D’EgidioC. AgostinelliS. VerrottiC. PavoneP. Diagnosis and management of catamenial seizures: A review.Int. J. Womens Health2012453554110.2147/IJWH.S28872 23071424
     [Google Scholar]
  7. QuiggM. SmithsonS.D. FowlerK.M. SursalT. HerzogA.G. Laterality and location influence catamenial seizure expression in women with partial epilepsy.Neurology200973322322710.1212/WNL.0b013e3181ae7adf 19620611
     [Google Scholar]
  8. CaligioniC.S. Assessing reproductive status/stages in mice.Curr. Protoc. Neurosci.20094814I10.1002/0471142301.nsa04is48 19575469
     [Google Scholar]
  9. StaleyK. ScharfmanH. A woman’s prerogative.Nat. Neurosci.20058669769910.1038/nn0605‑697 15917829
     [Google Scholar]
  10. HuangG.Z. WoolleyC.S. Estradiol acutely suppresses inhibition in the hippocampus through a sex-specific endocannabinoid and mGluR-dependent mechanism.Neuron201274580180810.1016/j.neuron.2012.03.035 22681685
     [Google Scholar]
  11. ScharfmanH. E. MacLuskyN. J. Sex differences in the neurobiology of epilepsy: A preclinical perspective.Neurobiol Dis.201472Pt B18019210.1016/j.nbd.2014.07.004
     [Google Scholar]
  12. WoolleyC.S. Acute effects of estrogen on neuronal physiology.Annu. Rev. Pharmacol. Toxicol.200747165768010.1146/annurev.pharmtox.47.120505.105219 16918306
     [Google Scholar]
  13. LiJ. LevertonL.K. NaganatanahalliL.M. Christian-HinmanC.A. Seizure burden fluctuates with the female reproductive cycle in a mouse model of chronic temporal lobe epilepsy.Exp. Neurol.202033411349210.1016/j.expneurol.2020.113492 33007292
     [Google Scholar]
  14. ClemensA.M. LenschowC. BeedP. LiL. SammonsR. NaumannR.K. WangH. SchmitzD. BrechtM. Estrus-cycle regulation of cortical inhibition.Curr. Biol.2019294605615.e610.1016/j.cub.2019.01.045 30744972
     [Google Scholar]
  15. AvoliM. ChenL.Y. Di CristoG. LibrizziL. ScalmaniP. ShiriZ. UvaL. de CurtisM. LévesqueM. Ligand-gated mechanisms leading to ictogenesis in focal epileptic disorders.Neurobiol. Dis.202318010609710.1016/j.nbd.2023.106097 36967064
     [Google Scholar]
  16. de CurtisM. AvoliM. GABA ergic networks jump‐start focal seizures.Epilepsia201657567968710.1111/epi.13370 27061793
     [Google Scholar]
  17. ElahianB. LadoN.E. MankinE. VangalaS. MisraA. MoxonK. FriedI. SharanA. YeasinM. StabaR. BraginA. AvoliM. SperlingM.R. EngelJ.Jr WeissS.A. Low‐voltage fast seizures in humans begin with increased interneuron firing.Ann. Neurol.201884458860010.1002/ana.25325 30179277
     [Google Scholar]
  18. KarunakaranS. GrasseD. W. MoxonK. A. Role of CA3 theta-modulated interneurons during the transition to spontaneous seizures.Exp Neurol.2016283Pt A34135210.1016/j.expneurol.2016.06.027
     [Google Scholar]
  19. LévesqueM. HerringtonR. HamidiS. AvoliM. Interneurons spark seizure-like activity in the entorhinal cortex.Neurobiol. Dis.2016879110110.1016/j.nbd.2015.12.011 26721318
     [Google Scholar]
  20. ScalmaniP. PaterraR. MantegazzaM. AvoliM. de CurtisM. Involvement of GABAergic interneuron subtypes in 4-Aminopyridine-induced seizure-like events in mouse entorhinal cortex in vitro.J. Neurosci.202343111987200110.1523/JNEUROSCI.1190‑22.2023 36810229
     [Google Scholar]
  21. AmilhonB. HuhC.Y.L. ManseauF. DucharmeG. NicholH. AdamantidisA. WilliamsS. Parvalbumin interneurons of hippocampus tune population activity at theta frequency.Neuron20158651277128910.1016/j.neuron.2015.05.027 26050044
     [Google Scholar]
  22. FennoL. YizharO. DeisserothK. The development and application of optogenetics.Annu. Rev. Neurosci.201134138941210.1146/annurev‑neuro‑061010‑113817 21692661
     [Google Scholar]
  23. YizharO. FennoL.E. DavidsonT.J. MogriM. DeisserothK. Optogenetics in neural systems.Neuron201171193410.1016/j.neuron.2011.06.004 21745635
     [Google Scholar]
  24. LiF.R. LévesqueM. WangS. Carreño-MuñozM.I. Di CristoG. AvoliM. Ictal activity is sustained by the estrogen receptor β during the estrous cycle.Curr. Res. Neurobiol.2024610013110.1016/j.crneur.2024.100131 38812499
     [Google Scholar]
  25. QuignonC. Collection and analysis of vaginal smears to assess reproductive stage in mice.Curr. Protoc.202339e88710.1002/cpz1.887 37725703
     [Google Scholar]
  26. YoungW.C. BolingJ.L. BlandauR.J. The vaginal smear picture, sexual receptivity and time of ovulation in the albino rat.Anat. Rec.1941801374510.1002/ar.1090800105
     [Google Scholar]
  27. LévesqueM. ChenL.Y. EtterG. ShiriZ. WangS. WilliamsS. AvoliM. Paradoxical effects of optogenetic stimulation in mesial temporal lobe epilepsy.Ann. Neurol.201986571472810.1002/ana.25572 31393618
     [Google Scholar]
  28. WangS. KfouryC. MarionA. LévesqueM. AvoliM. Modulation of in vitro epileptiform activity by optogenetic stimulation of parvalbumin-positive interneurons.J. Neurophysiol.2022128483784610.1152/jn.00192.2022 36043700
     [Google Scholar]
  29. BarbarosieM. AvoliM. CA3-driven hippocampal-entorhinal loop controls rather than sustains in vitro limbic seizures.J. Neurosci.199717239308931410.1523/JNEUROSCI.17‑23‑09308.1997 9364076
     [Google Scholar]
  30. OgnjanovskiN. SchaefferS. WuJ. MofakhamS. MaruyamaD. ZochowskiM. AtonS.J. Parvalbumin-expressing interneurons coordinate hippocampal network dynamics required for memory consolidation.Nat. Commun.2017811503910.1038/ncomms15039 28382952
     [Google Scholar]
  31. StarkE. EichlerR. RouxL. FujisawaS. RotsteinH.G. BuzsákiG. Inhibition-induced theta resonance in cortical circuits.Neuron20138051263127610.1016/j.neuron.2013.09.033 24314731
     [Google Scholar]
  32. StrüberM. SauerJ.F. BartosM. Parvalbumin expressing interneurons control spike-phase coupling of hippocampal cells to theta oscillations.Sci. Rep.2022121136210.1038/s41598‑022‑05004‑5 35079030
     [Google Scholar]
  33. AvoliM. BarbarosieM. LückeA. NagaoT. LopantsevV. KöhlingR. Synchronous GABA-mediated potentials and epileptiform discharges in the rat limbic system in vitro.J. Neurosci.199616123912392410.1523/JNEUROSCI.16‑12‑03912.1996 8656285
     [Google Scholar]
  34. AvoliM. LouvelJ. KurcewiczI. PumainR. BarbarosieM. Extracellular free potassium and calcium during synchronous activity induced by 4‐aminopyridine in the juvenile rat hippocampus.J. Physiol.1996493370771710.1113/jphysiol.1996.sp021416 8799893
     [Google Scholar]
  35. MorrisM.E. ObroceaG.V. AvoliM. ExtracellularK. Accumulations and synchronous gaba-mediated potentials evoked by 4-aminopyridine in the adult rat hippocampus.Exp. Brain Res.19961091718210.1007/BF00228628 8740210
     [Google Scholar]
  36. ShiriZ. ManseauF. LévesqueM. WilliamsS. AvoliM. Activation of specific neuronal networks leads to different seizure onset types.Ann. Neurol.201679335436510.1002/ana.24570 26605509
     [Google Scholar]
  37. KlausbergerT. MartonL.F. O’NeillJ. HuckJ.H.J. DaleziosY. FuentealbaP. SuenW.Y. PappE. KanekoT. WatanabeM. CsicsvariJ. SomogyiP. Complementary roles of cholecystokinin- and parvalbumin-expressing GABAergic neurons in hippocampal network oscillations.J. Neurosci.200525429782979310.1523/JNEUROSCI.3269‑05.2005 16237182
     [Google Scholar]
  38. KlausbergerT. MagillP.J. MártonL.F. RobertsJ.D.B. CobdenP.M. BuzsákiG. SomogyiP. Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo.Nature2003421692584484810.1038/nature01374 12594513
     [Google Scholar]
  39. ViitanenT. RuusuvuoriE. KailaK. VoipioJ. The K+–Cl− cotransporter KCC2 promotes GABAergic excitation in the mature rat hippocampus.J. Physiol.201058891527154010.1113/jphysiol.2009.181826 20211979
     [Google Scholar]
  40. FujitaS. ToyodaI. ThamattoorA.K. BuckmasterP.S. Preictal activity of subicular, CA1, and dentate gyrus principal neurons in the dorsal hippocampus before spontaneous seizures in a rat model of temporal lobe epilepsy.J. Neurosci.20143450166711668710.1523/JNEUROSCI.0584‑14.2014 25505320
     [Google Scholar]
  41. GrasseD.W. KarunakaranS. MoxonK.A. Neuronal synchrony and the transition to spontaneous seizures.Exp. Neurol.2013248728410.1016/j.expneurol.2013.05.004 23707218
     [Google Scholar]
  42. ToyodaI. FujitaS. ThamattoorA.K. BuckmasterP.S. Unit activity of hippocampal interneurons before spontaneous seizures in an animal model of temporal lobe epilepsy.J. Neurosci.201535166600661810.1523/JNEUROSCI.4786‑14.2015 25904809
     [Google Scholar]
  43. HerzogA.G. Catamenial epilepsy: Update on prevalence, pathophysiology and treatment from the findings of the NIH progesterone treatment trial.Seizure201528182510.1016/j.seizure.2015.02.024 25770028
     [Google Scholar]
/content/journals/cn/10.2174/011570159X326861241129093354
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Modulation of in vitro Network Activity by Optogenetic Stimulation of Parvalbumin-positive Interneurons During Estrous Cycle
Curr. Neuropharmacol. 23, 862 (2025); https://doi.org/10.2174/011570159X326861241129093354
/content/journals/cn/10.2174/011570159X326861241129093354
/content/journals/cn/10.2174/011570159X326861241129093354
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  • Article Type:     Research Article
Keyword(s): 4-aminopyridine; Catamenial epilepsy; estrous cycles; optogenetic stimulation; parvalbumin-positive interneurons; progesterone blood levels

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