Tunicamycin impairs olfactory learning and synaptic plasticity in the olfactory bulb
Tunicamycin impairs olfactory learning and synaptic plasticity in the olfactory bulb
复制标题
衣霉素损害嗅球的嗅觉学习和突触可塑性
DOI：
10.1016/j.neuroscience.2017.01.001
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发表时间：
2017
期刊：
影响因子：
3.3
通讯作者：
Kaba H
中科院分区：
文献类型：
--
作者：
Tong J;Okutani F;Murata Y;Taniguchi M;Namba T;Wang YJ;Kaba H
衣霉素（TM）诱导内质网（ER）应激并抑制细胞中的N-糖基化。ER应激与神经退行性疾病中的神经元死亡相关，例如帕金森病和阿尔茨海默病，并且大多数患者抱怨嗅觉识别受损。在这里，我们研究了TM对厌恶性嗅觉学习和主嗅球（MOB）的突触可塑性的影响。行为实验表明，眼球内注入TM禁用厌恶嗅觉学习，而不影响短期记忆。组织学分析显示，TM输液上调C/EBP同源蛋白（CHOP），ER应激的标志物，在二尖瓣和颗粒细胞层的MOB。电生理数据表明，TM抑制破伤风诱导的长时程增强（LTP）在树突兴奋性突触从二尖瓣颗粒细胞。低剂量TM（250 nM）可阻断LTP的晚期，高剂量TM（1 μM）可抑制LTP的早期和晚期。此外，高剂量，但不是低剂量，TM降低成对脉冲易化率，表明TM对LTP的抑制作用部分是通过突触前机制介导的。因此，我们的研究结果支持这一假设，TM诱导的内质网应激损害嗅觉学习通过抑制突触可塑性通过突触前和突触后机制在MOB。
Tunicamycin (TM) induces endoplasmic reticulum (ER) stress and inhibits N-glycosylation in cells. ER stress is associated with neuronal death in neurodegenerative disorders, such as Parkinson’s disease and Alzheimer’s disease, and most patients complain of the impairment of olfactory recognition. Here we examined the effects of TM on aversive olfactory learning and the underlying synaptic plasticity in the main olfactory bulb (MOB). Behavioral experiments demonstrated that the intrabulbar infusion of TM disabled aversive olfactory learning without affecting short-term memory. Histological analyses revealed that TM infusion upregulated C/EBP homologous protein (CHOP), a marker of ER stress, in the mitral and granule cell layers of MOB. Electrophysiological data indicated that TM inhibited tetanus-induced long-term potentiation (LTP) at the dendrodendritic excitatory synapse from mitral to granule cells. A low dose of TM (250 nM) abolished the late phase of LTP, and a high dose (1 μM) inhibited the early and late phases of LTP. Further, high-dose, but not low-dose, TM reduced the paired-pulse facilitation ratio, suggesting that the inhibitory effects of TM on LTP are partially mediated through the presynaptic machinery. Thus, our results support the hypothesis that TM-induced ER stress impairs olfactory learning by inhibiting synaptic plasticity via presynaptic and postsynaptic mechanisms in MOB.