Initiation of epileptiform activity in a rat model of periventricular nodular heterotopia

Naranzogt Tschuluun, H. Jürgen Wenzel, Emily T. Doisy, Philip A Schwartzkroin

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Purpose: Periventricular nodular heterotopia (PNH) is, in humans, often associated with difficult-to-control epilepsy. However, there is considerable controversy about the role of the PNH in seizure generation and spread. To study this issue, we have used a rat model in which injection of methylazoxymethanol (MAM) into pregnant rat dams produces offspring with nodular heterotopia-like brain abnormalities. Methods: Electrophysiologic methods were used to examine the activity of the MAM-induced PNH relative to activity in the neighboring hippocampus and overlying neocortex. Recordings were obtained simultaneously from these three structures in slice preparations from MAM-exposed rats and in intact animals. Bath application or systemic injection of bicuculline was used to induce epileptiform activity. Key Findings: In the in vitro slice, epileptiform discharge was generally initiated in hippocampus. In some cases, independent PNH discharge occurred, but the PNH never "led" discharges in hippocampus or neocortex. Intracellular recordings from PNH neurons confirmed that these cells received synaptic drive from both hippocampus and neocortex, and sent axonal projections to these structures-consistent with anatomic observations of biocytin-injected PNH cells. In intact animal preparations, bicuculline injection resulted in epileptiform discharge in all experiments, with a period of ictal-like electrographic activity typically initiated within 2-3 min after drug injection. In almost all animals, the onset of ictus was seen synchronously across PNH, hippocampal, and neocortical electrodes; in a few cases, the PNH electrode (histologically confirmed) did not participate, but in no case was activity initiated in the PNH electrode. Interictal discharge was also synchronized across all three electrodes; again, the PNH never "led" the other two electrodes, and typically followed (onset several milliseconds after hippocampal/neocortical discharge onset). Significance: These results do not support the hypothesis that the PNH lesion is the primary epileptogenic site, since it does not initiate or lead epileptiform activity that subsequently propagates to other brain regions.

Original languageEnglish (US)
Pages (from-to)2304-2314
Number of pages11
Issue number12
StatePublished - Dec 2011


  • Bicuculline
  • Cortical dysplasia
  • Electrographic seizure episode
  • Epileptic focus
  • Hippocampus
  • Interictal spikes
  • Neocortex

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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