Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
Mol Pain. 2014 Jan 8;10:1. doi: 10.1186/1744-8069-10-1.
The insular cortex (IC) is an important forebrain structure involved in pain perception and taste memory formation. Using a 64-channel multi-electrode array system, we recently identified and characterized two major forms of synaptic plasticity in the adult mouse IC: long-term potentiation (LTP) and long-term depression (LTD). In this study, we investigate injury-related metaplastic changes in insular synaptic plasticity after distal tail amputation. We found that tail amputation in adult mice produced a selective loss of low frequency stimulation-induced LTD in the IC, without affecting (RS)-3,5-dihydroxyphenylglycine (DHPG)-evoked LTD. The impaired insular LTD could be pharmacologically rescued by priming the IC slices with a lower dose of DHPG application, a form of metaplasticity which involves activation of protein kinase C but not protein kinase A or calcium/calmodulin-dependent protein kinase II. These findings provide important insights into the synaptic mechanisms of cortical changes after peripheral amputation and suggest that restoration of insular LTD may represent a novel therapeutic strategy against the synaptic dysfunctions underlying the pathophysiology of phantom pain.
脑岛皮层（IC）是参与疼痛感知和味觉记忆形成的重要前脑结构。使用 64 通道多电极阵列系统，我们最近在成年小鼠的 IC 中鉴定并描述了两种主要的突触可塑性形式：长时程增强（LTP）和长时程抑制（LTD）。在这项研究中，我们研究了远端尾巴切断后 IC 中与损伤相关的代谢变化。我们发现，成年小鼠尾巴切断后，IC 中低频刺激诱导的 LTD 选择性丧失，而不影响（RS）-3,5-二羟苯甘氨酸（DHPG）诱导的 LTD。用较低剂量的 DHPG 应用预先刺激 IC 切片可以在药理学上挽救受损的 IC LTD，这种代谢变化涉及蛋白激酶 C 的激活，但不涉及蛋白激酶 A 或钙/钙调蛋白依赖性蛋白激酶 II 的激活。这些发现为周围切断后皮质变化的突触机制提供了重要的见解，并表明恢复 IC LTD 可能代表一种治疗幻肢痛病理生理学下突触功能障碍的新策略。
