Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea; Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
Eur J Neurosci. 2013 Oct;38(8):3128-45. doi: 10.1111/ejn.12330. Epub 2013 Aug 11.
The insular cortex (IC) is known to play important roles in higher brain functions such as memory and pain. Activity-dependent long-term depression (LTD) is a major form of synaptic plasticity related to memory and chronic pain. Previous studies of LTD have mainly focused on the hippocampus, and no study in the IC has been reported. In this study, using a 64-channel recording system, we show for the first time that repetitive low-frequency stimulation (LFS) can elicit frequency-dependent LTD of glutamate receptor-mediated excitatory synaptic transmission in both superficial and deep layers of the IC of adult mice. The induction of LTD in the IC required activation of the N-methyl-d-aspartate (NMDA) receptor, metabotropic glutamate receptor (mGluR)5, and L-type voltage-gated calcium channel. Protein phosphatase 1/2A and endocannabinoid signaling are also critical for the induction of LTD. In contrast, inhibiting protein kinase C, protein kinase A, protein kinase Mζ or calcium/calmodulin-dependent protein kinase II did not affect LFS-evoked LTD in the IC. Bath application of the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine produced another form of LTD in the IC, which was NMDA receptor-independent and could not be occluded by LFS-induced LTD. Our studies have characterised the basic mechanisms of LTD in the IC at the network level, and suggest that two different forms of LTD may co-exist in the same population of IC synapses.
岛叶皮层（IC）已知在记忆和疼痛等高级脑功能中发挥重要作用。活动依赖性长时程抑制（LTD）是与记忆和慢性疼痛相关的主要突触可塑性形式。以前的 LTD 研究主要集中在海马体上，而在 IC 中没有报道。在这项研究中，我们使用 64 通道记录系统，首次表明重复的低频刺激（LFS）可引起成年小鼠 IC 的浅层和深层谷氨酸能受体介导的兴奋性突触传递的频率依赖性 LTD。IC 中 LTD 的诱导需要 N-甲基-D-天冬氨酸（NMDA）受体、代谢型谷氨酸受体（mGluR）5 和 L 型电压门控钙通道的激活。蛋白磷酸酶 1/2A 和内源性大麻素信号对于 LTD 的诱导也是至关重要的。相比之下，抑制蛋白激酶 C、蛋白激酶 A、蛋白激酶 Mζ 或钙/钙调蛋白依赖性蛋白激酶 II 不会影响 IC 中 LFS 诱导的 LTD。在 IC 中，应用 I 组 mGluR 激动剂（RS）-3,5-二羟基苯甘氨酸产生另一种 LTD 形式，该形式与 NMDA 受体无关，不能被 LFS 诱导的 LTD 阻断。我们的研究在网络水平上描述了 IC 中 LTD 的基本机制，并表明两种不同形式的 LTD 可能共存于相同的 IC 突触群体中。
