Transient ischemia induces an early decrease of synaptic transmission in CA1 neurons of rat hippocampus: electrophysiologic study in brain slices.
We examined the functionality of hippocampal CA1 neurons at early times after transient global ischemia, by electrophysiologic recordings in brain slices. Transient ischemia was conducted on rats using the method of 15-minute four-vessel occlusion, and brain slices were obtained from these animals at different times after ischemia. Within 24 hours after insult, CA1 neurons showed no substantial damage as identified by morphologic means, but exhibited dramatic decreases in synaptic activities by 12 hours after insult, which became further decreased at more extended times after recovery. Blocking gamma-aminobutyric acid A (GABAA) receptors with bicuculline produced a reversible augmentation of the diminished synaptic responses in slices prepared from 12-hour postinsult animals, but failed to do so in slices obtained from rats 24 hours after insult. Recorded in whole-cell mode, the minimum depolarizing current required to elicit an action potential was about twofold larger in the ischemic CA1 neurons than in sham controls, suggesting that an elevated spiking threshold exists in these neurons. We suggest that decreases in electrophysiologic activities precede the morphologic deterioration in postischemic CA1 neurons. The early decrease in CA1 synaptic activities may be associated with an imbalance between glutamate-mediated synaptic excitation and GABAA-mediated synaptic inhibition, whereas substantial impairments in synaptic transmission likely take place after prolonged post-ischemic recovery.
Shinno
K
K
Playfair Neuroscience Unit, Toronto Hospital Research Institute, Ontario, Canada.
Zhang
L
L
Eubanks
J H
JH
Carlen
P L
PL
Wallace
M C
MC
D000818:Animals; D004594:Electrophysiology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission