Hippocampus versus entorhinal cortex decoupling by an NR2 subunit-specific block of NMDA receptors in a rat in vitro model of temporal lobe epilepsy

Nicola Berretta, Ada Ledonne, Dalila Mango, Giorgio Bernardi, Nicola B. Mercuri

Research output: Contribution to journalArticle

Abstract

The role of N-methyl-d-aspartate receptors (NMDARs) in the generation and maintenance of epileptic seizures has been widely investigated, however, little is known of possible separate roles played by NMDARs that contain different NR2 subunits. A better comprehension of how distinct NMDARs subtypes participate in seizure generation and/or diffusion may lead to the development of more targeted pharmacologic strategies to treat epilepsy. Therefore, we have performed an electrophysiologic investigation using a multielectrode array device, on slices comprising entorhinal cortex (EC) and hippocampus, continuously perfused in a Mg 2+-free medium, with added 4-aminopiridine (4AP; 10-15 μm). Two separate rhythmic patterns of interictal-like activity were generated in EC and hippocampus, with EC seizures entrained to those in CA3, so that a significant degree of cross-correlation occurred. Perfusion with the NR2A-containing NMDAR antagonist [(R)-[(S)-1-(4-bromo-phenyl)-ethylamino]-(2,3-dioxo-1,2,3,4- tetrahydroquinoxalin-5-yl)-methyl]-phosphonic acid (NVP-AAM077; 50 nm) or Zn 2+ (200 nm), did not affect the rate of interictal-like events in EC and hippocampus; however, it significantly reduced their cross-correlation, causing a substantial decoupling of the two rhythm generators. The same effect was observed with (αR,βS)-α-(4-hydroxyphenyl)-β-methyl-4- (phenylmethyl)-1-piperidinepropanol maleate (Ro25-6981; 1 μm), when coapplied with a subthreshold dose of NVP-AAM077. Our results suggest that NR2 subunits may be crucial in entraining cortical networks, leading to recruitment of wider range oscillations during epilepsy. Therefore, a pharmacologic strategy directed onto NR2 subunits may help to limit seizure diffusion and recruitment of potentially entrained oscillatory networks.

Original languageEnglish
JournalEpilepsia
Volume53
Issue number5
DOIs
Publication statusPublished - May 2012

Fingerprint

Entorhinal Cortex
Temporal Lobe Epilepsy
N-Methyl-D-Aspartate Receptors
Hippocampus
Epilepsy
Seizures
Perfusion
Maintenance
Equipment and Supplies
aspartic acid receptor
In Vitro Techniques
5-(alpha-methyl-4-bromobenzylamino)phosphonomethyl-1,4-dihydroquinoxaline-2,3-dione

Keywords

  • Cross-correlation
  • Multielectrode array
  • NR2 subunits

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Hippocampus versus entorhinal cortex decoupling by an NR2 subunit-specific block of NMDA receptors in a rat in vitro model of temporal lobe epilepsy. / Berretta, Nicola; Ledonne, Ada; Mango, Dalila; Bernardi, Giorgio; Mercuri, Nicola B.

In: Epilepsia, Vol. 53, No. 5, 05.2012.

Research output: Contribution to journalArticle

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