The Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) mediates long-term potentiation or depression (LTP or LTD) after distinct stimuli of hippocampal NMDA-type glutamate receptors (NMDARs). NMDAR-dependent LTD prevails in juvenile mice, but a mechanistically different form of LTD can be readily induced in adults by instead stimulating metabotropic glutamate receptors (mGluRs). However, the role that CaMKII plays in the mGluR-dependent form of LTD is not clear. Here we show that mGluR-dependent LTD also requires CaMKII and its T286 autophosphorylation (pT286), which induces Ca²⁺-independent autonomous kinase activity. In addition, we compared the role of pT286 among three forms of long-term plasticity (NMDAR-dependent LTP and LTD, and mGluR-dependent LTD) using simultaneous live imaging of endogenous CaMKII together with synaptic marker proteins. We determined that after LTP stimuli, pT286 autophosphorylation accelerated CaMKII movement to excitatory synapses. After NMDAR-LTD stimuli, pT286 was strictly required for any movement to inhibitory synapses. Similar to NMDAR-LTD, we found the mGluR-LTD stimuli did not induce CaMKII movement to excitatory synapses. However, in contrast to NMDAR-LTD, we demonstrate that the mGluR-LTD did not involve CaMKII movement to inhibitory synapses and did not require additional T305/306 autophosphorylation. Thus, despite its prominent role in LTP, we conclude that CaMKII T286 autophosphorylation is also required for both major forms of hippocampal LTD, albeit with differential requirements for the heterosynaptic communication of excitatory signals to inhibitory synapses.

Ca ²⁺ /钙调蛋白依赖性蛋白激酶 II (CaMKII) 在海马 NMDA 型谷氨酸受体 (NMDAR) 的不同刺激后介导长期增强或抑制 (LTP 或 LTD)。NMDAR 依赖性 LTD 在幼年小鼠中普遍存在，但通过刺激代谢型谷氨酸受体 (mGluR) 可以很容易地在成年小鼠中诱导出一种机制上不同的 LTD。然而，CaMKII 在依赖于 mGluR 的 LTD 形式中所起的作用尚不清楚。在这里，我们表明依赖于 mGluR 的 LTD 还需要 CaMKII 及其 T286 自身磷酸化 (pT286)，从而诱导 Ca ²⁺-独立的自主激酶活性。此外，我们使用内源性 CaMKII 和突触标记蛋白的同时实时成像比较了 pT286 在三种形式的长期可塑性（依赖于 NMDAR 的 LTP 和 LTD 和依赖于 mGluR 的 LTD）中的作用。我们确定在 LTP 刺激后，pT286 自身磷酸化加速了 CaMKII 向兴奋性突触的运动。在 NMDAR-LTD 刺激后，任何抑制性突触的运动都严格要求 pT286。与 NMDAR-LTD 类似，我们发现 mGluR-LTD 刺激不会诱导 CaMKII 运动到兴奋性突触。然而，与 NMDAR-LTD 相比，我们证明 mGluR-LTD 不涉及 CaMKII 向抑制性突触的运动，并且不需要额外的 T305/306 自磷酸化。因此，尽管它在 LTP 中发挥着重要作用，