Brain plasticity and remodeling of AMPA receptor properties by calcium-dependent enzymes

Long-term potentiation (LTP) and long-term depression (LTD) are two experimental models of synaptic plasticity that have been studied extensively in the last 25 years, as they may represent basic mechanisms to store certain types of information in neuronal networks. In several brain regions, these two forms of synaptic plasticity require dendritic depolarization, and the amplitude and duration of the depolarization-induced calcium signal are crucial parameters for the generation of either LTP or LTD. The rise in calcium concentration mediated by activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors has been proposed to stimulate various calcium-dependent processes that could convert the induction signal into long-lasting changes in synaptic structure and function. According to several lines of experimental evidence, alterations in synaptic function observed with LTP and LTD are thought to be the result of modifications of postsynaptic currents mediated by the a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptors. The question of which type(s) of receptor changes constitutes the basis for the expression of synaptic plasticity is still very much open. Here, we review data relevant to the issue of selective modulation of AMPA receptor properties occurring after learning and memory, environmental enrichment, and synaptic plasticity. We also discuss potential cellular mechanisms whereby calcium-dependent enzymes might regulate AMPA receptor properties during LTP and LTD, focusing on protein kinases, proteases and lipases.