SPATIAL EXPLORATION INDUCES A PERSISTENT REVERSAL OF LONG-TERM POTENTIATION IN RAT HIPPOCAMPUS

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.