Bidirectional multisite seizure propagation in the intact isolated hippocampus: The multifocality of the seizure "focus"

M. Derchansky, D. Rokni, J. T. Rick, R. Wennberg, B. L. Bardakjian, L. Zhang, Y. Yarom, P. L. Carlen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Localizing the seizure focus is difficult and frequently, multiple sites are found. This reflects our poor understanding of the fundamental mechanisms of seizure generation and propagation. We used multisite electrophysiological recordings in two seizure models and voltage-sensitive dye imaging, to spatiotemporally characterize the initiation and propagation of seizures in an intact epileptogenic brain region, the isolated hippocampus. In low-magnesium perfusate, seizures always originated in the temporal region, and propagated along the septotemporal axis to the septal region. After the seizure spread across the hippocampus, the bursts within a seizure became bidirectional, with different propagation patterns at different frequencies. When the intact hippocampus was separated along the septotemporal axis, independent bidirectional activity was observed in the two halves, and region-specific cuts to the tissue reveal that the CA3 region is critical for seizure generation and propagation. In a second seizure model, using focal tetanic stimulation of the septal and temporal CA3 region, seizures always originated at the stimulated site with bidirectionality later developing at different frequencies, as noted in the low magnesium model, behavior compatible with coupled neuronal network oscillators. These data provide novel insights into the dynamic multifocality of seizure onset and propagation, revealing that the current concept of a single seizure "focus" is complex.

Original languageAmerican English
Pages (from-to)312-328
Number of pages17
JournalNeurobiology of Disease
Volume23
Issue number2
DOIs
StatePublished - Aug 2006

Bibliographical note

Funding Information:
This study is supported by CIHR, the Krembil Scientist Development Seed Fund, the Savoy Epilepsy Foundation, CURE and the Israel Science Foundation. We would like to thank Hanoch Meiri, Puah Mann-Metzer, Adam Charlinski, Damian Shin, Michael Moddel and Frank Vidic for their technical assistance and Helen Scharfman for her help with the review of the manuscript.

Keywords

  • Bidirectionality
  • CA3 region
  • Epilepsy
  • Hippocampus
  • Longitudinal slice
  • Network oscillators
  • Propagation
  • Seizures
  • Septotemporal Axis
  • Voltage-sensitive dyes

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