The influence of high frequency, repetitive transcranial magnetic stimulation on long-term potentiation in the hippocampus and on spatial learning and memory after global cerebral ischemia

Abstract

Objective To investigate the effects of repeated high frequency transcranial magnetic stimulation (rTMS) on spatial learning and memory function,and on long-term potentiation (LTP) after global cerebral ischemia and reperfusion,and to explore the mechanisms involved.Methods Eighty-three male Wistar rats were studied.Five were tested to determine their average motor threshold (Tm).The others were divided into a normal control group,a cerebral ischemia and reperfusion model group and an rTMS group.Cerebral ischemia was induced with the four vessel occlusion method for 10 minutes.The rTMS treatment protocol (10 Hz stimulation for 5 s at the resting threshold,twice a day) was applied over a 2-week period from day 3 post-operation.The Morris water maze test was performed to observe spatial learning and memory at post-operation day 2 and day 4.The field excitatory postsynaptic potentials,population spike and the magnitude of long-term potentiation (LTP) induced by theta burst electric stimulation were recorded from the perforant path to the dentate gyrus (PP-DG).Results At post-operation day 3,rats in the untreated cerebral ischemia and reperfusion model group exhibited a significant decrease in the magnitude of the PP-DG LTP as compared to the normal group.No significant difference in LTP was found between the model group and the rTMS group.After the 2 weeks of treatment the LTP levels in the rTMS treated group were significantly higher than in the two untreated groups.In the Morris water maze testing,the average escape latency in the rTMS group was significantly shorter than that of the cerebral ischemia and reperfusion model group (which was not treated).In the probe trials,the time in the original quadrant of the platform and the time of crossing the platform were both significantly less for the rTMS-treated rats than for those not treated.Conclusions High frequency rTMS can improve spatial learning and memory after global cerebral ischemia and reperfusion by enhancing the LTP induced in the hippocampus.High frequency rTMS might exert this beneficial effect by modulating the function of intermediate neurons in the hippocampal neuronal network and by promoting neurotransmitter release. Key words: Transcranial magnetic stimulation; Cerebral ischemia; Spatial learning; Memory; Long-term potentiation