The anterior cingulate cortex (ACC) is a key cortical region for pain perception and emotion. Different forms of synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), have been reported in the ACC. Synaptic tagging of LTP plays an important role in hippocampus-related associative memory. In this study, we demonstrate that synaptic tagging of LTD is detected in the ACC of adult male and female mice. This form of tagged LTD requires the activation of metabotropic glutamate receptor subtype 1 (mGluR1). The induction of tagged LTD is time-related with the strongest tagged LTD appearing when the interval between two independent stimuli is 30 min. Inhibitors of mGluR1 blocked the induction of tagged LTD; however, blocking N-methyl-d-aspartate receptors did not affect the induction of tagged LTD. Nimodipine, an inhibitor of L-type voltage–gated calcium channels, also blocked tagged LTD. In an animal model of amputation, we found that tagged LTD was either reduced or completely blocked. Together with our previous report of tagged LTP in the ACC, this study strongly suggests that excitatory synapses in the adult ACC are highly plastic. The biphasic tagging of synaptic transmission provides a new form of heterosynaptic plasticity in the ACC which has functional and pathophysiological significance in phantom pain.

前扣带皮层（ACC）是疼痛感知和情绪的关键皮质区域。 ACC 中已报道了不同形式的突触可塑性，包括长时程增强 (LTP) 和长时程抑制 (LTD)。 LTP 的突触标记在海马相关的联想记忆中发挥着重要作用。在这项研究中，我们证明了在成年雄性和雌性小鼠的 ACC 中检测到 LTD 的突触标记。这种形式的标记 LTD 需要激活代谢型谷氨酸受体亚型 1 (mGluR1)。标记LTD的诱导与时间相关，当两个独立刺激之间的间隔为30分钟时出现最强的标记LTD。 mGluR1 抑制剂阻断标记 LTD 的诱导；然而，阻断N-甲基-d-天冬氨酸受体并不影响标记LTD的诱导。尼莫地平 (Nimodipine) 是一种 L 型电压门控钙通道抑制剂，也能阻断标记的 LTD。在截肢动物模型中，我们发现标记的LTD要么减少，要么完全阻断。结合我们之前关于 ACC 中标记 LTP 的报告，这项研究强烈表明成人 ACC 中的兴奋性突触具有高度可塑性。突触传递的双相标记在 ACC 中提供了一种新形式的异质突触可塑性，这在幻痛中具有功能和病理生理学意义。