Figure 11.

Illustration of molecular pathways involved in presynaptic mfLTP induction. During repetitive activation of mossy fibers, Ca²⁺ accumulates in presynaptic nerve terminals outside of the immediate area of the active zone, thereby activating adenylate cyclase (AC) via calmodulin. Adenylate cyclase activation increases the presynaptic levels of cAMP which in turn activates protein kinase-A which phosphorylates Syt12 and possibly other targets. These targets then cooperate with RIM1α and Rab3A to increase the efficacy of the neurotransmitter release machinery, thereby producing a long-lasting enhancement of neurotransmitter release.