Figure 2.

Presynaptic form of long-term potentiation (LTP). The best-studied example of the presynaptic NMDA receptor–independent LTP is the mossy fiber synapse on CA3 hippocampal pyramidal neurons. In this case, NMDA receptor activation is not required for LTP induction. The most important changes in this form of synaptic plasticity happen in the presynaptic bouton leading to increased neurotransmitter release after tetanic stimulation. The molecular mechanism involves activation of multiple kinases including protein kinase (PK) A and PKC. Phosphorylation of synapsin releases synaptic vesicles from the actin cytoskeleton. Mobilized vesicles bind to the active zone and undergo priming to become ready for release. This process can be facilitated by RIM1, munc13, and munc18 protein phosphorylation. Activated RIM protein attracts the scaffold protein of 14-3-3 and thus could create new landing regions for vesicles. Synaptic vesicle delivery is accelerated by the activated GTP bound form of rab3 small G protein, probably by shedding its binding partner, rabphilin. Primed vesicles undergo fusion when elevated intracellular calcium levels trigger SNARE complex (synaptobrevin2/VAMP2, syntaxin1, and SNAP-25) activation via binding to the calcium sensor synaptotagmin on the primed vesicle. Increased neurotransmitter release is detected as larger excitatory postsynaptic potential amplitude. For clarity, the endocytosis part of synaptic vesicle cycle was omitted.