Recent studies demonstrate that calcitonin gene-related peptide (CGRP) plays critical roles in migraine. Immunohistochemistry and in situ hybridization studies have shown that CGRP and its receptors are expressed in cortical areas that are critical for pain perception including the anterior cingulate cortex (ACC) and insular cortex (IC). Recent studies reported that CGRP enhanced excitatory transmission in the ACC. However, little is known about the possible effect of CGRP on excitatory transmission in the IC. In the present study, we investigated the role of CGRP on synaptic transmission in the IC slices of adult male mice. Bath application of CGRP produced dose-dependent potentiation of evoked excitatory postsynaptic currents (eEPSCs). This potentiation was NMDA receptor (NMDAR) independent. After application of CGRP1 receptor antagonist CGRP8-37 or BIBN 4096, CGRP produced potentiation was significantly reduced. Paired-pulse facilitation was significantly decreased by CGRP, suggesting possible presynaptic mechanisms. Consistently, bath application of CGRP significantly increased the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs). By contrast, amplitudes of sEPSCs and mEPSCs were not significantly affected. Finally, adenylyl cyclase subtype 1 (AC1) and protein kinase A (PKA) are critical for CGRP-produced potentiation, since both selective AC1 inhibitor NB001 and the PKA inhibitor KT5720 completely blocked the potentiation. Our results provide direct evidence that CGRP contributes to synaptic potentiation in the IC, and the AC1 inhibitor NB001 may be beneficial for the treatment of migraine in the future.

中文翻译：

---

降钙素基因相关肽（CGRP）在成年小鼠的岛皮质中诱导的皮质增强。

最近的研究表明降钙素基因相关肽（CGRP）在偏头痛中起关键作用。免疫组织化学和原位杂交研究表明，CGRP及其受体在对疼痛感至关重要的皮质区域表达，包括前扣带回皮质（ACC）和岛状皮质（IC）。最近的研究报道，CGRP增强了ACC中的兴奋性传递。但是，关于CGRP对IC中兴奋性传递的可能影响知之甚少。在本研究中，我们调查了CGRP在成年雄性小鼠IC切片中突触传递中的作用。CGRP的沐浴应用可产生诱发兴奋性突触后突触电流（eEPSC）的剂量依赖性增强作用。该增强作用是不依赖NMDA受体（NMDAR）的。应用CGRP1受体拮抗剂CGRP8-37或BIBN 4096后，CGRP产生的增强作用显着降低。CGRP显着降低了配对脉冲的促进作用，提示可能存在突触前机制。一致地，CGRP的沐浴应用显着增加了自发性和微型兴奋性突触后电流（sEPSC和mEPSC）的频率。相比之下，sEPSC和mEPSC的幅度并未受到明显影响。最后，腺苷酸环化酶亚型1（AC1）和蛋白激酶A（PKA）对于CGRP产生的增强作用至关重要，因为选择性AC1抑制剂NB001和PKA抑制剂KT5720都完全阻断了这种增强作用。我们的结果提供了直接的证据，表明CGRP有助于IC中的突触增强，