THE LONG-TERM SUPPRESSIVE EFFECT OF PRIOR ACTIVATION OF SYNAPTIC INPUTS BY LOW-FREQUENCY STIMULATION ON INDUCTION OF LONG-TERM POTENTIATIONIN CA1 NEURONS OF GUINEA-PIG HIPPOCAMPAL SLICES

We have investigated the effects of prior activation of afferent input s by a train of low-frequency stimulation (LFS) on the induction of lo ng-term potentiation (LTP) induced by high-frequency stimulation (teta nus, 100 Hz, 100 pulses) in CA1 neurons of guinea pig hippocampal slic es. The parameters of the LFS were altered systematically: the frequen cy (1 or 5 Hz); the number of pulses (80, 200 or 1000); and the time l ag from the LFS to the tetanus (20, 60 or 100 min). Conditioning effec ts of the LFS on the induction of LTP were evaluated in terms of the s lope of the field excitatory postsynaptic potential (S-EPSP) and the a mplitude of the population spike (A-PS). LTP could reliably be induced by 100 Hz tetanic stimulation delivered to a naive slice. In contrast , the attempt to induce LTP 60 min after LFS of 200 or 1000 pulses at 1 Hz resulted only in short-term potentiation while the LFS itself pro duced no significant change in the responses. The suppressive effect o n LTP was significantly reduced for 1 Hz LFS with a smaller number of pulses (80 pulses), or a shorter (20 min) or longer (100 min) time lag from the LFS to the tetanus, or with LFS at a higher frequency (5 Hz) . When the LFS of 1000 pulses at 1 Hz was delivered in the presence of the N-methyl-D-aspartate (NMDA) receptor antagonist AP5 (D,L-4-amino- 5-phosphonovalerate, 50 mu M), which was washed out after the end of t he LFS, the tetanus given 60 min after application of the LFS produced stable LTP, indicating the involvement of NMDA receptor/channels in t he mechanisms of this particular form of synaptic plasticity - long-te rm suppression of LTP.