Protein kinases: which one is the memory molecule?

Encoding of new experiences is likely to induce activity-dependent modifica tions in the brain. Studies in organisms far apart on the phylogenetic scal e have shown that similar, sometimes identical, signal transduction pathway s subserve plasticity in neuronal systems, and they may play pivotal roles in the formation of long-term memories. It has become evident that phosphor ylation/dephosphorylation reactions are critical for the initiation of cell ular mechanisms that embody, retain and modify information in neural circui ts. Although physiological investigations on synaptic plasticity have had a major impact, we have concentrated our review on behavioural studies that provide direct or indirect evidence for a role of kinases in mechanisms und erlying memory formation. From these, it appears that the learning event in duces activation of a variety of kinases with specific time courses. For in stance, the calcium/calmodulin-dependent protein kinase II seems to partici pate in an early phase of memory formation. Apparently, activation of both protein tyrosine kinases and mitogen-activated protein kinases is required for much longer and may thus have a particular function during transformati on from short-term into long-term memory. Quite different time courses appe ar for protein kinase C (PKC) and protein kinase A (PKA), which may functio n at two different time points, shortly after training and again much later . This suggests that PKC and PKA might play a role at early and late stages of memory formation. However, we have considered some examples showing tha t these signalling pathways do not function in isolation but rather interac t in an intricate intracellular network. This is indicative of a more compl ex contribution of each kinase to the fine tuning of encoding and informati on processing. To decipher this complexity, pharmacological, biochemical an d genetic investigations are more than ever necessary to unravel the role o f each kinase in the syntax of learning and memory formation.