Permanent Reduction of Seizure Threshold in Post-Ischemic CA3 Pyramidal Neurons

J Neurophysiol. 2000 Apr;83(4):2040-6. doi: 10.1152/jn.2000.83.4.2040.

Abstract

The effects of ischemia were examined on CA3 pyramidal neurons recorded in hippocampal slices 2-4 mo after a global forebrain insult. With intracellular recordings, CA3 post-ischemic neurons had a more depolarized resting membrane potential but no change of the input resistance, spike threshold and amplitude, fast and slow afterhyperpolarization (AHP) or ADP, and firing properties in response to depolarizing pulses. With both field and whole-cell recordings, synaptic responses were similar in control and post-ischemic neurons. Although there were no spontaneous network-driven discharges, the post-ischemic synaptic network had a smaller threshold to generate evoked and spontaneous synchronized burst discharges. Thus lower concentrations of convulsive agents (kainate, high K(+)) triggered all-or-none network-driven synaptic events in post-ischemic neurons more readily than in control ones. Also, paired-pulse protocol generates, in post-ischemics but not controls, synchronized field burst discharges when interpulse intervals ranged from 60 to 100 ms. In conclusion, 2-4 mo after the insult, the post-ischemic CA3 pyramidal cells are permanently depolarized and have a reduced threshold to generate synchronized bursts. This may explain some neuropathological and behavioral consequences of ischemia as epileptic syndromes observed several months to several years after the ischemic insult.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Brain Ischemia / complications
  • Brain Ischemia / physiopathology*
  • Epilepsy / etiology
  • Epilepsy / physiopathology*
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / cytology
  • Hippocampus / physiopathology*
  • In Vitro Techniques
  • Kainic Acid / pharmacology
  • Male
  • Patch-Clamp Techniques
  • Periodicity
  • Potassium / pharmacology
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Wistar
  • Seizures / etiology
  • Seizures / physiopathology
  • Stimulation, Chemical
  • Synapses / physiology
  • Time Factors

Substances

  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Potassium
  • Kainic Acid