Erythropoietin decreases the excitatory neurotransmitter release probability and enhances synaptic plasticity in mice hippocampal slices

Abstract In order to examine the direct acute effect of erythropoietin (EPO) perfusion on synaptic plasticity and transmitter release probability in hippocampal slices, one month old mice were decapitated and hippocampal slices were prepared. The effect of EPO perfusion (50 U/ml) on the basic synaptic transmission of hippocampal slices was examined. In addition, paired-pulse facilitation (PPF with inter stimulus intervals ISI of 50, 100 and 200 ms), long term potentiation (LTP) and depression (LTD) were recorded using high (HFS) and low (LFS) frequency stimulations. EPO-perfusion depressed significantly the slope of the fEPSP. The PPF ratio was increased significantly when compared with pre-EPO-perfusion. Stimulation of the control slices with LFS (1 Hz) depressed significantly the slope of the fEPSP (77.7 ± 3.85% of the baseline responses). Intermediate stimulation frequency (10 Hz) produced no significant changes, while HFS (100 Hz) induced significant potentiation of the responses (142.38 ± 7.72%). In EPO-perfused slices significant bigger responses were obtained (1 Hz, 101.12 ± 5.69%, 10 Hz, 123.24 ± 2.68, and 100 Hz, 216.41 ± 20.1) when compared to the control slices. These results suggest that erythropoietin decreases the excitatory neurotransmitter release probability and may in this way protect the synapses from toxic levels of glutamate. Erythropoietin perfusion increased the expression of long-term potentiation in the hippocampus which is considered as basic cellular model for learning and memory.