Figure 1.

Thrombin induces long-term potentiation of reactivity to afferent stimulation and saturates tetanus-induced LTP. A, B, Application of thrombin (1 U/ml; A) as well as the PAR1 receptor agonist, PAR1-AP (B), produces a gradual increase in population EPSP in stratum radiatum CA1, without affecting population presynaptic volleys (top traces). C, Thrombin-induced LTP is blocked by the PAR1 receptor antagonist SCH79797, which does not affect tetanic LTP. D, Thrombin induces LTP in a naive pathway without affecting an already saturated pathway, which was previously exposed to three tetanic stimulations. E, A short (10 min) application of thrombin produces a saturating LTP; a tetanic stimulation to the same pathway, adjusted to submaximal level (downward arrow), is able to produce a short-term but not a long-term potentiation. F, Once thrombin-induced LTP has been established, it cannot be blocked by later application of SCH79797, nor could it be further potentiated by a second sustained application of the drug, applied to an adjusted response level (downward arrow). G, Low concentration of PAR1-AP amplifies the ability of a short tetanic stimulation to produce LTP. Short tetanic stimulation applied before PAR1-AP was able to produce a short-lasting but no long-lasting potentiation. PAR1-AP at a low concentration (0.5 μm) did not affect responses to the stimulation, but was able to convert a short into a long-lasting potentiation to short stimulation applied later. H, Thrombin-induced LTP is partially blocked by application of the NR2B antagonist, ifenprodil, as is the potentiation produced by the tetanic stimulation. I, The NMDA antagonist APV totally blocks thrombin-induced LTP, but after washout of the drug, tetanic LTP is completely normal. Averaged EPSP slopes are plotted versus time. Representative traces at indicated times (a, b) are shown on top of each section. Upward arrows indicate the time of HFS.