Related Experiment Video
Updated: Jul 20, 2026
Targeting the Corticospinal Tract in Neonatal Rats with a Double-Viral Vector using Combined Brain and Spine Surgery
Published on: June 30, 2021
NR2B antagonists restrict spatiotemporal spread of activity in a rat model of cortical dysplasia
Susanta Bandyopadhyay1, John J Hablitz
1Department of Neurobiology and Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
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 microM) 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 microM) and ifenprodil (10 microM). 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 microM) reduced activity evoked in presence of 50 microM 4-aminopyridine (known to increase excitability by enhancing neurotransmitter release) in neocortical slices from control animals whereas Ro 25-6981 (1 microM) 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.
Insights
NR2B subunit-containing N-methyl-D-aspartate receptors (NMDARs) drive abnormal brain activity in a rat model of focal cortical dysplasia. Selective NMDAR antagonists reduced this hyperexcitability, offering potential therapeutic targets for epilepsy.
Area of Science:
- Neuroscience
- Epilepsy Research
- Neuronal Migration Disorders
Background:
- Freeze-lesion-induced focal cortical dysplasia in rats mimics human microgyria, a condition linked to drug-resistant epilepsy.
- Altered N-methyl-D-aspartate receptors (NMDARs), particularly those with NR2B subunits, are implicated in the hyperexcitability observed in this epilepsy model.
Purpose of the Study:
- To investigate the role of NR2B subunit-containing NMDARs in the enhanced neuronal activity characteristic of the rat freeze-lesion model of focal cortical dysplasia.
- To evaluate the efficacy of selective NR2B NMDAR antagonists in modulating this abnormal activity.
Main Methods:
- Whole-cell voltage-clamp recordings were performed on pyramidal cells in brain slices from freeze-lesioned and control rats.
- Voltage-sensitive dye imaging was employed to analyze the spatiotemporal spread of evoked neuronal activity.
- The effects of selective NR2B antagonists (Ro 25-6981, ifenprodil) and a non-selective NMDAR antagonist (APV) were assessed.
Main Results:
- The NR2B-selective antagonist Ro 25-6981 significantly reduced the response area of evoked postsynaptic currents in the affected cortical area of lesioned rats.
- Bath application of Ro 25-6981 and ifenprodil decreased the peak amplitude, duration, and lateral spread of evoked activity in the lesioned cortex.
- Neither Ro 25-6981 nor ifenprodil affected neuronal activity in control (sham-operated) animals, indicating target specificity.
Conclusions:
- NR2B subunit-containing NMDARs play a critical role in the enhanced spatiotemporal spread of paroxysmal activity in the rat model of focal cortical dysplasia.
- Targeting NR2B-containing NMDARs with selective antagonists presents a promising therapeutic strategy for managing drug-resistant epilepsy associated with focal cortical dysplasia.
More Related Videos
09:22A Method for Remotely Silencing Neural Activity in Rodents During Discrete Phases of Learning
Published on: June 22, 2015
08:22A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
Published on: December 1, 2017