Permanent reduction of seizure threshold in post-ischemic CA3 pyramidal neurons

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