SYNAPTIC METAPLASTICITY AND THE LOCAL CHARGE EFFECT IN POSTSYNAPTIC DENSITIES

Synaptic plasticity might be one of the elementary processes that unde rlies higher brain functions, such as learning and memory. Intriguingl y, the capacity of a synapse for plastic changes itself displays marke d variation or plasticity. This higher-order plasticity, or metaplasti city, appears to depend on the same macromolecules as plasticity, most notably the NMDA receptor and Ca2+/calmodulin kinase II; yet we do no t understand metaplasticity in molecular terms. Metaplasticity has a f eedback-inhibition character that confers stability to synaptic patter ns, whereas in plasticity, the molecular events implicated tend to hav e an opposite effect. As a resolution to this difference, we suggest t hat metaplasticity be considered in a biophysical context. It has been shown that autophosphorylation of Ca2+/calmodulin kinase II in postsy naptic densities generates changes in the local electrostatic potentia l sufficient to affect the direction of synaptic plasticity. We propos e that this finding could help explain both the puzzling abundance of Ca2+/calmodulin kinase II in the postsynaptic density and the metaplas ticity of synaptic transmission.