The roles of protein kinases in learning and memory.

In the adult mammalian brain, more than 250 protein kinases are expressed, but only a few of these kinases are currently known to enable learning and memory. Based on this information it appears that learning and memory-related kinases either impact on synaptic transmission by altering ion channel properties or ion channel density, or regulate gene expression and protein synthesis causing structural changes at existing synapses as well as synaptogenesis. Here, we review the roles of these kinases in short-term memory formation, memory consolidation, memory storage, retrieval, reconsolidation, and extinction. Specifically, we discuss the roles of calcium/calmodulin-dependent kinase II (CaMKII), the calcium/calmodulin kinase cascade, extracellular signal regulated kinase 1 and 2 (ERK1/2), cAMP-dependent protein kinase A (PKA), cGMP-dependent protein kinase G (PKG), the phosphatidylinositol 3-kinase (PI3K) pathway, and protein kinase M ζ (PKMζ). Although these kinases are important for learning and memory processes, much remains to be learned as to how they act. Therefore, it will be important to identify and characterize the critical phosphorylation substrates so that a sophisticated understanding of learning and memory processes will be achieved. This will also allow for a systematic analysis of dysfunctional kinase activity in mental disorders.