Presynaptic occlusion of NMDA receptor-dependent potentiation in Synaptophysin family knockouts

Baseline synaptic strength is elevated in knockouts missing the synaptophysin family of synaptic vesicle proteins because of increased probability of release of release-ready vesicles. Here we show that the longest lasting component of long-term potentiation (LTP) is: (a) eliminated at Schaffer collateral synapses under standard conditions; (b) rescued by reducing extracellular Ca2+ enough to lower baseline synaptic strength to wildtype levels; and, (c) eliminated at wildtype synapses by increasing Ca2+ enough to elevate baseline to knockout levels. Next, an earlier component of LTP, lasting less than 1 hr, was eliminated first at knockouts and then wildtype by elevating baseline further. And, the LTP that was eliminated could be recovered by subsequently reducing extracellular Ca2+ back to the permissive level. In sum, NMDA receptor-dependent LTP maintenance and expression are separable mechanisms at extensively studied Schaffer collateral synapses, and expression of multiple components can be occluded by enhancing the mechanism that catalyzes synaptic vesicle exocytosis from presynaptic terminals.