Differential effects of long-term Potentiation evoked at the CA3-CA1 synapse before, during, and after the acquisition of classical eyeblink conditioning in behaving mice

Experimentally induced long-term potentiation (LTP) is a persistent increase in synaptic strength that decays across time. In contrast, changes in synaptic strength during actual learning are gradual processes that increase with training. We have studied here the effects of LTP evoked before, during, and after the acquisition of a well known associative learning paradigm: the classical eyeblink conditioning. We used a trace paradigm, with a tone as the conditioned stimulus (CS) and an electric shock presented to the supraorbital nerve as the unconditioned stimulus (US). A single electrical pulse was presented to the Schaffer collateral-commissural pathway to evoke field EPSPs (fEPSPs) during the CS-US interval. LTP induced by high-frequency stimulation of the Schaffer collaterals lasted for 6-10 d. When LTP was evoked before conditioning, animals were unable to acquire conditioned eyeblinks if the training started 8 d after LTP disappearance, and no change was detected in fEPSP evoked at the CA3-CA1 synapse during conditioning. In contrast, LTP-induced animals learned as did controls when the conditioning test was presented 20 d after LTP had decayed to baseline, and presented a normal increase in fEPSP slopes across conditioning. When evoked during the first two conditioning sessions, LTP prevented both eyeblink conditioning and fEPSP increase. Finally, LTP did not disrupt the normal performance of a recall test of a previously acquired eyeblink conditioning. In this latter experiment, both the LTP-induced potentiation of fEPSPs and their physiological potentiation decayed across time with a similar time constant, with no apparent effect on memory recall.