Metabotropic Glutamate Receptor Subtype 7 Ablation Causes Deficit in Fear Response and Conditioned Taste Aversion
Metabotropic Glutamate Receptor Subtype 7 Ablation Causes Deficit in Fear Response and Conditioned Taste Aversion
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代谢型谷氨酸受体亚型 7 消融导致恐惧反应和条件性味觉厌恶缺陷
作者：
M. Masugi;M. Yokoi;R. Shigemoto;K. Muguruma;Yasuyoshi Watanabe;G. Sansig;H. van der Putten;S. Nakanishi
代谢型谷氨酸受体（mGluRs）由八种不同的亚型组成，并通过G蛋白对第二信使和离子通道发挥作用。然而，个别mGluR亚型在CNS中的功能在很大程度上仍有待澄清。我们检查了野生型和mGluR 7-/-敲除的同窝小鼠在电击后结冰的恐惧反应。野生型小鼠表现出冻结后立即和1天后足休克。相比之下，mGluR 7 −/−敲除小鼠在休克后即刻和延迟冻结反应中的水平均显着降低。然而，敲除小鼠在疼痛敏感性和运动活动方面没有表现出异常。为了进一步研究杏仁核依赖的行为，我们进行了条件性味觉厌恶（CTA）实验。在野生型小鼠中，糖精给药后腹腔注射萎靡不振诱导剂LiCl导致糖精和LiCl之间的关联。这种关联导致对糖精的强烈CTA。相比之下，mGluR 7 −/−敲除小鼠在CTA实验中未能将味觉和阴性味觉联系起来。同样，敲除小鼠在味觉偏好和对LiCl毒性的敏感性方面没有表现出异常。这些结果表明，mGluR 7缺乏导致两个不同的杏仁核依赖的行为模式的损害。免疫组织化学和免疫电镜分析表明，mGluR 7是高度表达的杏仁核和优先定位于突触前轴突终末的mGluR 7能神经元。总之，这些研究结果强烈表明，mGluR 7参与神经过程subserving杏仁核依赖的厌恶反应。
Metabotropic glutamate receptors (mGluRs) consist of eight different subtypes and exert their effects on second messengers and ion channels via G-proteins. The function of individual mGluR subtypes in the CNS, however, largely remains to be clarified. We examined the fear response of freezing after electric shock in wild-type and mGluR7−/− knockout littermates. Wild-type mice displayed freezing immediately after and 1 d after footshock. In comparison, mGluR7−/− knockout mice showed significantly reduced levels in both immediate postshock and delayed freezing responses. However, the knockout mice exhibited no abnormalities in pain sensitivity and locomotor activity. To further examine amygdala-dependent behavior, we performed conditioned taste aversion (CTA) experiments. In wild-type mice, the administration of saccharin followed by intraperitoneal injection of the malaise-inducing agent LiCl resulted in an association between saccharin and LiCl. This association caused strong CTA toward saccharin. In contrast, mGluR7−/− knockout mice failed to associate between the taste and the negative reinforcer in CTA experiments. Again, the knockout mice showed no abnormalities in taste preference and in the sensitivity to LiCl toxicity. These results indicate that mGluR7 deficiency causes an impairment of two distinct amygdala-dependent behavioral paradigms. Immunohistochemical and immunoelectron-microscopic analyses showed that mGluR7 is highly expressed in amygdala and preferentially localized at the presynaptic axon terminals of glutamatergic neurons. Together, these findings strongly suggest that mGluR7 is involved in neural processes subserving amygdala-dependent averse responses.
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