NR2B antagonists restrict spatiotemporal spread of activity in a rat model of cortical dysplasia

Academic Article

Abstract

  • Freeze-lesion-induced focal cortical dysplasia in rats closely resembles human microgyria, a neuronal migration disorder associated with drug-resistant epilepsy. Alterations in expression of N-methyl-d-aspartate receptors (NMDARs) containing NR2B subunits have been suggested to play a role in the hyperexcitability seen in this model. We examined the effect of NMDAR antagonists selective for NR2B subunits (Ro 25-6981 and ifenprodil) on activity evoked by intracortical stimulation in brain slices from freeze-lesioned rat neocortex. Whole-cell voltage-clamp recordings showed that Ro 25-6981 (1 μM) significantly reduced the response area of evoked postsynaptic currents in pyramidal cells from the paramicrogyral area whereas responses were unaffected in slices from control (sham operated) animals. Voltage-sensitive dye imaging was used to examine spatiotemporal spread of evoked activity in lesioned and control cortices. The imaging experiments revealed that peak amplitude, duration, and lateral spread of evoked activity in the paramicrogyral area was reduced by bath application of Ro 25-6981 (1 μM) and ifenprodil (10 μM). Ro 25-6981 had no effect on evoked activity in neocortical slices from control animals. The non-selective NMDAR antagonist d-2-amino-5-phosphonvaleric acid (APV, 20 μM) reduced activity evoked in presence of 50 μM 4-aminopyridine (known to increase excitability by enhancing neurotransmitter release) in neocortical slices from control animals whereas Ro 25-6981 (1 μM) did not. These results suggest that NR2B subunit-containing NMDARs contribute significantly to the enhanced spatiotemporal spread of paroxysmal activity observed in vitro in the rat freeze-lesion model of focal cortical dysplasia. © 2006 Elsevier B.V. All rights reserved.
  • Authors

    Published In

  • Epilepsy Research  Journal
  • Digital Object Identifier (doi)

    Author List

  • Bandyopadhyay S; Hablitz JJ
  • Start Page

  • 127
  • End Page

  • 139
  • Volume

  • 72
  • Issue

  • 2-3