Stable mossy fiber long-term potentiation requires calcium influx at the granule cell soma, protein synthesis, and microtubule-dependent axonal transport.

The synapses formed by the mossy fiber (MF) axons of hippocampal dentate gyrus granule neurons onto CA3 pyramidal neurons exhibit an intriguing form of experience-dependent synaptic plasticity that is induced and expressed presynaptically. In contrast to most other CNS synapses, long-term potentiation (LTP) at the MF-CA3 synapse is readily induced even during blockade of postsynaptic glutamate receptors. Furthermore, blocking voltage-gated Ca(2+) channels prevents MF-LTP, supporting an involvement of presynaptic Ca(2+) signaling via voltage-gated Ca(2+) channels in MF-LTP induction.

Hippocampal synaptic metaplasticity requires inhibitory autophosphorylation of Ca2+/calmodulin-dependent kinase II.

Virtually all CNS synapses display the potential for activity-dependent long-term potentiation (LTP) and/or long-term depression (LTD). Intriguingly, the potential to exhibit LTP or LTD at many central synapses itself is powerfully modulated by previous synaptic activity. This higher-order form of plasticity has been termed metaplasticity.