The Ca²⁺/calmodulin (CaM)-dependent protein kinase II (CaMKII) plays a fundamental role in learning and possibly also in memory. However, current mechanistic models require fundamental revision. CaMKII autophosphorylation at Thr286 (pThr286) does not provide the molecular basis for long-term memory, as long believed. Instead, pThr286 mediates the signal processing required for induction of several distinct forms of synaptic plasticity, including Hebbian long-term potentiation and depression and non-Hebbian behavioral timescale synaptic plasticity. We discuss (i) the molecular computations by which CaMKII supports these diverse plasticity mechanisms, (ii) alternative CaMKII mechanisms that may contribute to the maintenance phase of LTP and (iii) the relationship of these mechanisms to behavioral learning and memory.

Ca²⁺/钙调蛋白 （CaM） 依赖性蛋白激酶 II （CaMKII） 在学习和记忆中起着重要作用。然而，当前的机理模型需要从根本上修改。Thr286 （pThr286） 位点的 CaMKII 自磷酸化并不像长期以来认为的那样为长期记忆提供分子基础。相反，pThr286 介导诱导几种不同形式的突触可塑性所需的信号处理，包括 Hebbian 长期增强和抑制以及非 Hebbian 行为时间尺度突触可塑性。我们讨论了 （i） CaMKII 支持这些不同可塑性机制的分子计算，（ii） 可能有助于 LTP 维持阶段的替代 CaMKII 机制，以及 （iii） 这些机制与行为学习和记忆的关系。