Bayer Karl Ulrich, Giese Karl Peter
Department of Pharmacology and Program in Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Department of Basic and Clinical Neuroscience, King's College London, London, UK.
Nat Neurosci. 2025 Jan;28(1):24-34. doi: 10.1038/s41593-024-01809-x. Epub 2024 Nov 18.
The Ca/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.
钙/钙调蛋白（CaM）依赖性蛋白激酶II（CaMKII）在学习过程中起着基础性作用，在记忆方面可能也发挥着作用。然而，目前的机制模型需要进行根本性修正。长期以来人们认为，CaMKII在苏氨酸286位点（pThr286）的自身磷酸化是长期记忆的分子基础。但事实并非如此，相反，pThr286介导了诱导多种不同形式突触可塑性所需的信号处理过程，包括赫布型长时程增强和抑制以及非赫布型行为时间尺度突触可塑性。我们讨论了：（i）CaMKII支持这些多样可塑性机制的分子计算方式；（ii）可能有助于长时程增强维持阶段的CaMKII替代机制；以及（iii）这些机制与行为学习和记忆的关系。
