Synaptic maturation and tagging between early and late long-term potentiation-induced synapses

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Accumulating evidence has suggested pivotal roles for neural proteases in cognitive functions. Among such proteases, neuropsin, a kallikrein gene-related(KLK) endoprotease, appears to have a significant plasticity function that has been analyzed primarily in the hippocampal Schaffer-collateral pathway. Enzymatically active neuropsin is necessary to establish the early phase of long-term potentiation(LTP). Associations between early and persistent-LTP synapses may be related to mammalian working memory and consequently integration in learning and memory(Ishikawa et al). We challenged and succeeded to obtaining specific substrate for protease neuropsin and found that neuregulin-1 is the most suitable native substrate for neuropsin(Tamura et al). Novel signaling pathway of neuropsin-neuregulin might be a significant in mammalian cognition.