Effect of transient ischemia on long-term potentiation of synaptic transmission in rat hippocampal slices.

Objectives: Long-term potentiation (LTP) of neuronal activity in the hippocampus is thought to be a substrate for learning and memory. The influence of ischemia (IS) (hypoxia/hypoglycemia) on induction of LTP of synaptic transmission (ST) by high frequency stimulation (HFS) was investigated in rat hippocampal slices.

Methods: Neurons were stimulated via Schäffer collaterals and field excitatory postsynaptic potentials (fEPSP) were recorded extracellularly from the CA1 region. LTP was induced by one single train (100 Hz, 1s).

Results: In controls LTP of ST after HFS was 179.70+/-12.53%. Short IS of 2.5-4.5 min elicited a transient failure of ST, with return to former value followed by further increase of fEPSP amplitude to 142.28+/-16.24%, compared to amplitude before IS. HFS was elicited 40 min after exposure to IS and LTP was measured over further 40-60 min. LTP in slices exposed to 2.5-4.5-min IS was 139.94+/-14.01%. IS of 6-7.5 min elicited a prolonged failure of ST, with almost full recovery (96.69+/-14.42%). LTP was not activated 40 min after 6-7.5-min IS and the amplitude of fEPSP was even reduced to 80.14+/-19.19% compared to the former mean value of fEPSP 10 min before HFS.

Conclusion: The results revealed that prolonged 6-7.5-min IS influenced induction of LTP of ST in the hippocampus and thus it could have deleterious effects on learning and memory. These findings may have clinical implications in stroke, brain ischemia, sleep apnoe and call for studying the effect of neuroprotectants on the induction of LTP in hippocampus exposed to oxidative stress.