Synaptic metaplasticity and the local charge effect in postsynaptic densities.

Synaptic plasticity might be one of the elementary processes that underlies higher brain functions, such as learning and memory. Intriguingly, the capacity of a synapse for plastic changes itself displays marked variation or plasticity. This higher-order plasticity, or metaplasticity, appears to depend on the same macromolecules as plasticity, most notably the NMDA receptor and Ca2+/calmodulin kinase II; yet we do not understand metaplasticity in molecular terms. Metaplasticity has a feedback-inhibition character that confers stability to synaptic patterns, whereas in plasticity, the molecular events implicated tend to have an opposite effect. As a resolution to this difference, we suggest that metaplasticity be considered in a biophysical context. It has been shown that autophosphorylation of Ca2+/calmodulin kinase II in postsynaptic densities generates changes in the local electrostatic potential sufficient to affect the direction of synaptic plasticity. We propose that this finding could help explain both the puzzling abundance of Ca2+/calmodulin kinase II in the postsynaptic density and the metaplasticity of synaptic transmission.