Inhibition of long-term potentiation by low frequency stimulation in the perforant pathway – dentate gyrus synapses

Objective: Long-term potentiation (LTP) and depression can be considered in terms of the relationship of stimulation frequency and resultant change in synaptic plasticity. Low-frequency stimulation (LFS) given before induction of LTP inhibits LTP without affecting either basal synaptic strength or the early phase of LTP. This anterograde inhibitory effect of LFS is persistent and is blocked by inhibitors of phosphatases. Herein, we investigated the effect of LFS on subsequent LTP magnitude using four different stimulus frequencies. Methods: The study used four groups of adult Wistar rats. The effect of different stimulation patterns (0.5-Hz, 1-Hz, 2-Hz and 5 Hz, n=8/ group) designed to induce long-lasting depression of the perforant pathway inputs to the dentate gyrus on subsequently induced LTP was investigated. All paradigms consisted of 900 pulses. LTP was induced by a strong tetanisation protocol and measured as 5-min average of excitatory-postsynaptic potential (EPSP) and population spike (PS) 5 min and 60 min after its induction. LTP magnitude was compared using one-way ANOVA test. Results: The input-output curves of the groups were comparable to each other, as shown by the non-significant interaction observed between stimulus intensity and frequency. We found hat 0.5-Hz, but not 5-Hz, stimulation inhibited for 60 min the subsequent induction of fEPSP-LTP by a normally efficient LTP-inducing protocol. There was significant difference in PS LTP between two groups at two measurement intervals (p<0.001) and positive correlations between LTP magnitudes and frequencies. Conclusion: These data indicate that certain patterns of LFS can activate different intracellular molecular cascades, and that longlasting activation of phosphatases by prior LFS can suppress the subsequent expression of LTP. We suggest that this form of metaplasticity may influence information storage by modulating the capacity of synapses to express LTP after repeated bouts of activity.