Experiments in which several high and/or low frequency stimulation pat
terns were applied to different groups of afferents in CA1 hippocampal
slices revealed the existence of heterosynaptic interactions between
LTP and LTD. Specifically, we report that repeated induction of LTD on
one input was associated with a heterosynaptic reversal of the LTP pr
eviously induced on a separate pathway. Reapplication of high frequenc
y stimulation at the end of the experiment reinstated LTP. This hetero
synaptic reversal occurred without modification of naive responses, an
d it was prevented by D-AP5, an NMDA receptor antagonist, or cyclospor
in A, a calcineurin inhibitor. Similarly, induction of LTP on one inpu
t was found to reverse hetero-synaptically the LTD previously induced
on a separate pathway. This effect was also sensitive to D-AP5, it occ
urred without modification of naive pathways, and LTD could be reinsta
ted by low frequency trains. These results indicate that repeated indu
ction of LTP or LTD on one group of afferents can reset synaptic effic
acy at other nonactivated synapses.