Immature Status Epilepticus: In Vitro Models Reveal Differences in Cholinergic Control and HFO Properties of Adult CA3 Interictal Discharges in Temporal vs Septal Hippocampus

Research output: Contribution to journalArticle

Abstract

We have earlier demonstrated that a Status Epilepticus (SE) during CNS development has long-lasting effects on cholinergic neurotransmission, detectable in vitro and in vivo. In this work, we aimed to localize changes in temporal (T) vs septal (S) hippocampus and to correlate adult CA3 interictal epileptiform discharge (IED) frequency changes to those of Ripples (R) and Fast Ripples (FR) of the High-Frequency Oscillations (HFOs). Spontaneous IEDs were induced by bathing slices in Mg2+-free ACSF or in 4-Aminopyridine (4-AP, 50 µM) and data were analyzed separately for each model. IED frequencies were similar in same origin normal (N) slices across models, but differed in SE slices, being lower in Mg2+-free ACSF than in 4-AP, suggesting a post-SE long-term increase in a K+ conductance. Rs and FRs detected within IEDs had generally higher power in 4-AP than in Mg2+-free ACSF; FR/R ratio was the highest in T-SE slices in 4-AP and similar in all other slice groups. Carbachol or eserine increased IED rates universally, but had region- and conditioning-specific effects on HFOs, suggesting that IED frequency and HFOs represent possibly independent indices of excitability. The muscarinic antagonist atropine depressed IED rates with increasing effectiveness in S slices post-SE in both models. In conclusion, the long-term effects of an immature SE are region-specific within the hippocampus, affect differently synchronizing components like the IED frequency and HFOs and may shape neurotransmitter effects (ACh) on neuronal networks, thus affecting seizure threshold and information processing, especially in behavioral conditions of rising extracellular ACh levels.

Details

Authors
External organisations
  • University of Ioannina
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology

Keywords

  • high-frequency oscillations, interictal, muscarinic, seizures, septal hippocampus, temporal hippocampus
Original languageEnglish
Pages (from-to)386-398
Number of pages13
JournalNeuroscience
Volume369
Publication statusPublished - 2018 Jan 15
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes