Seizure-like activity and cellular damage in rat hippocampal neurons in cell culture

Neuron. 1989 Aug;3(2):199-207. doi: 10.1016/0896-6273(89)90033-0.


Neurons dissociated from the hippocampal formations of neonatal rats were grown in medium containing kynurenic acid (a glutamate receptor antagonist) and elevated Mg2+. Such chronically blocked neurons, when first exposed to medium without blockers (after 0.5-5.0 months), generated intense seizure-like activity. This consisted of bursts of synchronous electrical responses that resembled paroxysmal depolarization shifts and sustained depolarizations that, in some neurons, nearly abolished the resting potential. Sustained depolarizations were usually reversed by timely application of kynurenate or 2-amino-5-phosphonovalerate, indicating that continuous activation of glutamate receptors was required for their maintenance. Prolonged periods of intense seizure-like activity usually killed most neurons in the culture. This system allows seizure-related cellular mechanisms to be studied in long-term cell culture.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Survival / physiology
  • Cells, Cultured
  • Electric Conductivity / drug effects
  • Electric Conductivity / physiology
  • Hippocampus / cytology*
  • Hippocampus / physiopathology
  • Hippocampus / ultrastructure
  • Kynurenic Acid / pharmacology
  • Magnesium / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neurons / cytology*
  • Neurons / physiology
  • Neurons / ultrastructure
  • Rats
  • Receptors, Glutamate
  • Receptors, Neurotransmitter / drug effects
  • Seizures / physiopathology*


  • Receptors, Glutamate
  • Receptors, Neurotransmitter
  • Kynurenic Acid
  • Magnesium