Stable depression of potentiated synaptic responses in the hippocampus with 1-5 Hz stimulation.

Adult rats with two chronic stimulating electrodes in the Schaffer collateral/commissural system of the hippocampus and one recording electrode in the stratum radiatum (apical dendrites) of field CA1 were administered high-frequency stimulation (10 brief bursts at theta frequency) to produce long-term potentiation (LTP). 'Low frequency' stimulation (100 pulses at 1 Hz alone or followed by 250 pulses at 5 Hz) delivered 5-15 min later had no effect on LTP in 18% of the rats, caused a transient reversal in 18% of the group, but produced an apparent reversal of LTP for the remainder of a 1 h test session in 64% of the animals. LTP did not recover in animals tested 24 h later, at which point a second episode of high-frequency stimulation but without subsequent low-frequency stimulation was administered. This produced an LTP effect that persisted for a 1 h test session in 94% of the cases and that was still present in 86% of the animals tested 24 h later. Low-frequency stimulation applied prior to induction of LTP had no lasting effects on evoked responses not did it affect responses to a control stimulating electrode in those cases in which it reversed LTP. Possible implications of these results for hypotheses concerning the substrates of LTP and mechanisms of forgetting are discussed.