Pii: S0306-4522(99)00265-1

Long-term changes in synaptic transmission in slices of rat visual cortex were induced either by pairing the excitatory postsynaptic potentials with postsynaptic depolarization or by intracellular tetanization without synaptic stimulation. Changes in the excitatory postsynaptic potential amplitude induced by any of the protocols applied in isolation persisted for longer than 1 h. Pairing-induced long-term potentiation was input specific. We studied the interaction between intracellular tetanization and pairing-induced plasticity by applying the two protocols one after the other at 10-min intervals. The pairing procedure applied after intracellular tetanization did not lead to any further potentiation, but to a depotentiation of the potentiated inputs. A second pairing protocol applied 10 min later led to further depotentiation, while previously unaffected inputs became weakly depressed. If intracellular tetanization was applied after the pairing procedure, the synaptic responses did not change immediately, but a slow return of the excitatory postsynaptic potential amplitude to the control level could be observed. Therefore, intracellular tetanization is not capable of inducing further potentiation after pairing, and pairing cannot further potentiate the inputs which have already been potentiated by intracellular tetanization. The maintenance of long-term potentiation induced by any of the protocols was impaired by successive application of another procedure. These results suggest a similarity of the mechanisms of synaptic changes induced by the two protocols and demonstrate that the direction of synaptic gain change depends on the history of the synapse. q 1999 IBRO. Published by Elsevier Science Ltd.