Low frequency perforant path stimulation as a conditioned stimulus demonstrates correlations between long-term synaptic potentiation and learning.

Stimulation of the perforant path with impulse trains of 15 cps and 670 msec duration was used as a conditioned stimulus in a two-way shuttle box avoidance on rats. Field potentials in the dentate area evoked by test stimuli were measured after the training sessions until the 7th day. Foot-shock and unconditioned escape elicited only a transient slight depression of the population spike amplitude (P) and increased also slightly the slope function (SF) of the population EPSP of the evoked test potentials. The control stimulation of the perforant path without pairing with foot-shock as in conditioning did only slightly increase SF of test potentials, but produced a strong transient inhibition followed by a long lasting moderate depression of P. After conditioning, all animals exhibited the same initial inhibition of P as shown in control stimulation of the perforant path. However during the following 4 hours, good learners with a relearning index greater than 30% developed a significant potentiation of P lasting until the second training session 24 hours later, which resulted in a further enhancement. SF of the evoked test potentials increased in good learners with a similar time course after conditioning but without initial depression. After 7 days P showed still enhanced but non-significant values. Poor learners with a relearning index less than 10% did not develop a potentiation of P after conditioning and initial inhibition, but a long-term depression. Also SF of test potentials decreased in poor learners during 4 hours after conditioning and returned almost to baseline until the following day. After 7 days, P and SF did not differ from baseline. The analysis of the observed synaptic changes by E-S curves demonstrated the post-tetanic LTP seems to differ in some ways from post-conditioning LTP in good learners. The latter exhibits a clear tendency of a right shift contrary to the left shift commonly occurring after tetanization. Furthermore poor learners do not only fail to produce long-term potentiation, but fail to show a change in the opposite direction with a left shift of the E-S curves. The observed correlation of LTP in the conditioning pathway with the learning ability suggests an involvement of LTP at least in the acquisition and early retention of this learned behavior. The results do however not finally clarify the role of LTP in long-term retention.