Experience-dependent long-lasting increases in excitatory synaptic tra
nsmission in the hippocampus are believed to underlie certain types of
memory(1-3). Whereas stimulation of hippocampal pathways in freely mo
ving rats can readily elicit a long-term potentiation (LTP) of transmi
ssion that may last for weeks, previous studies have failed to detect
persistent increases in synaptic efficacy after hippocampus-mediated l
earning(4-6). As changes in synaptic efficacy are contingent on the hi
story of plasticity at the synapses(7), we have examined the effect of
experience-dependent hippocampal activation on transmission after the
induction of LTP, We show that exploration of a new, non-stressful en
vironment rapidly induces a complete and persistent reversal of the ex
pression of high-frequency stimulation-induced early-phase LTP in the
CA1 area of the hippocampus, without affecting baseline transmission i
n a control pathway. LTP expression is not affected by exploration of
familiar environments. We found that spatial exploration affected LTP
within a defined time window because neither the induction of LTP nor
the maintenance of long-established LTP was blocked. The discovery of
a novelty-induced reversal of LTP expression provides strong evidence
that extensive long-lasting decreases in synaptic efficacy may act in
tandem with enhancements at selected synapses to allow the detection a
nd storage of new information by the hippocampus.