The 4-aminopyridine in vitro epilepsy model analyzed with a perforated multi-electrode array

Alfredo Gonzalez Sulser, Jing Wang, Gholam K. Motamedi, Massimo Avoli, Stefano Vicini, Rhonda Dzakpasu

Research output: Contribution to journalArticlepeer-review

Abstract

Epileptiform discharges recorded in the 4-aminopyridine (4-AP) in vitro epilepsy model are mediated by glutamatergic and GABAergic signaling. Using a 60-channel perforated multi-electrode array (pMEA) on corticohippocampal slices from 2 to 3 week old mice we recorded interictal- and ictal-like events. When glutamatergic transmission was blocked, interictal-like events no longer initiated in the hilus or CA3/CA1 pyramidal layers but originated from the dentate gyrus granule and molecular layers. Furthermore, frequencies of interictal-like events were reduced and durations were increased in these regions while cortical discharges were completely blocked. Following GABA(A) receptor blockade interictal-like events no longer propagated to the dentate gyrus while their frequency in CA3 increased; in addition, ictal-like cortical events became shorter while increasing in frequency. Lastly, drugs that affect tonic and synaptic GABAergic conductance modulated the frequency, duration, initiation and propagation of interictal-like events. These findings confirm and expand on previous studies indicating that multiple synaptic mechanisms contribute to synchronize neuronal network activity in forebrain structures.

This article is part of a Special Issue entitled 'Trends in Neuropharmacology: In Memory of Erminio Costa'. (C) 2010 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1142-1153
Number of pages12
JournalNeuropharmacology
Volume60
Issue number7-8
DOIs
Publication statusPublished - Jun 2011

Keywords

  • Seizures
  • Hippocampus
  • 4-Aminopyridine
  • Local field potentials
  • GABA
  • JUVENILE RAT HIPPOCAMPUS
  • TEMPORAL-LOBE EPILEPSY
  • GABA(A) RECEPTOR
  • TONIC INHIBITION
  • INTERNEURONS
  • DISCHARGES
  • POTENTIALS
  • MECHANISMS
  • CORTEX

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