Metabotropic Glutamate Receptor Subtype 7 in the Bed Nucleus of the Stria Terminalis is Essential for Intermale Aggression
Metabotropic Glutamate Receptor Subtype 7 in the Bed Nucleus of the Stria Terminalis is Essential for Intermale Aggression
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DOI：
10.1038/npp.2015.198
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发表时间：
2016-02-01
影响因子：
7.6
通讯作者：
Kawata, Mitsuhiro
中科院分区：
文献类型：
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作者：
Masugi-Tokita, Miwako;Flor, Peter J.;Kawata, Mitsuhiro
代谢型谷氨酸受体亚型7（mGluR 7）是III组mGluR的成员，其定位于哺乳动物中枢神经系统的突触前活性区。虽然组织学、遗传学和电生理学研究确保了mGluR 7的重要性，但其在行为和生理学中的作用仍然很大程度上未知。使用居民入侵者范例，我们发现mGluR 7敲除（KO）小鼠的雄性间攻击行为严重减少。我们还发现雄性mGluR 7基因敲除小鼠的其他社会行为发生了变化，包括对男性入侵者的性行为。由于嗅觉对啮齿动物的社会行为（包括攻击性）至关重要，我们进行了嗅觉测试，发现mGluR 7 KO小鼠对雄性尿液的气味没有表现出兴趣。为了阐明嗅觉缺陷，我们随后将小鼠暴露于尿液并分析c-Fos免疫反应性，发现mGluR 7 KO小鼠的终纹（BNST）床核中的神经活动显著减少。最后，BNST内给予mGluR 7选择性拮抗剂6-（4-甲氧基苯基）-5-甲基-3-吡啶-4-基异恶唑并[4，5-c]吡啶-4（5 H）-酮（MMPIP）也重现了mGluR 7 KO小鼠的表型，包括攻击性降低和社会互动改变。因此mGluR 7可能在BNST中作为“神经活动的增强剂”工作，并且对雄性间的攻击很重要。我们的研究结果表明，mGluR 7是必不可少的社会行为和先天行为。我们对BNST中mGluR 7的研究将为人类情感障碍的未来治疗提供启示。
Metabotropic glutamate receptor subtype 7 (mGluR7) is a member of group III mGluRs, which localize to the presynaptic active zones of the mammalian central nervous system. Although histological, genetic, and electrophysiological studies ensure the importance of mGluR7, its roles in behavior and physiology remain largely unknown. Using a resident-intruder paradigm, we found a severe reduction in intermale aggressive behavior in mGluR7 knockout (KO) mice. We also found alterations in other social behaviors in male mGluR7 KO mice, including sexual behavior toward male intruders. Because olfaction is critical for rodent social behavior, including aggression, we performed an olfaction test, finding that mGluR7 KO mice failed to show interest in the smell of male urine. To clarify the olfactory deficit, we then exposed mice to urine and analyzed c-Fos-immunoreactivity, discovering a remarkable reduction in neural activity in the bed nucleus of the stria terminalis (BNST) of mGluR7 KO mice. Finally, intra-BNST administration of the mGluR7-selective antagonist 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5-c] pyridin-4(5H)-one (MMPIP) also reproduced the phenotype of mGluR7 KO mice, including reduced aggression and altered social interaction. Thus mGluR7 may work as an 'enhancer of neural activity' in the BNST and is important for intermale aggression. Our findings demonstrate that mGluR7 is essential for social behavior and innate behavior. Our study on mGluR7 in the BNST will shed light on future therapies for emotional disorders in humans.