Subtype-selective contribution of muscarinic acetylcholine receptors for filial imprinting in newly-hatched domestic chicks
Subtype-selective contribution of muscarinic acetylcholine receptors for filial imprinting in newly-hatched domestic chicks
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DOI：
10.1016/j.bbr.2022.113789
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发表时间：
2022-02-14
影响因子：
2.7
通讯作者：
Homma, Koichi J.
中科院分区：
文献类型：
--
作者：
Aoki, Naoya;Mori, Chihiro;Homma, Koichi J.
毒蕈碱型乙酰胆碱受体（mAChRs）在许多脑功能中起重要作用。我们以前的研究表明，mAChRs拮抗剂东莨菪碱注射到中间内侧中皮层（IMM）区域，这是关键的子代印迹，损害记忆的形成。在鸟类脑中，已经鉴定出四种mAChR亚型（M-2、M-3、M-4和M-5）。M-3和M-5受体增加神经元的兴奋性，而M-2和M-4受体降低神经元的兴奋性。由于东莨菪碱阻断所有亚型，先前的研究没有确定哪种亚型有助于记忆的形成。通过将几种类型的mAChR拮抗剂注射到IMM中，在这项研究中，我们确定哪种mAChR亚型在印迹中起关键作用。首先，检查拮抗剂对兴奋性受体亚型M-3和M-5的作用。注射20 mM的M-3拮抗剂（DAU 5884）或2 mM的M-5拮抗剂（ML 381）会损害印迹。考虑到DAU 5884的pKi值，损伤似乎是由DAU 5884与M-3和/或M-4受体结合引起的。第二，检查拮抗剂对抑制性受体亚型M-2的作用。结果表明，M-2拮抗剂AQ-RA 741在20 mM浓度下可使印迹功能受损，结合AQ-RA 741的pKi值，推测其可能是与M-2和/或M-4结合所致。这项研究的结果表明，兴奋性受体亚型M-3和M-5和抑制性受体亚型M-2和/或M-4合作，以实现适当的平衡乙酰胆碱信号执行印迹。
Muscarinic acetylcholine receptors (mAChRs) play an important role in many brain functions. Our previous study revealed that the injection of mAChRs antagonist scopolamine into the intermediate medial mesopallium (IMM) region, which is critical for filial imprinting, impairs memory formation. In avian brains, four mAChR subtypes have been identified (M-2, M-3, M-4 and M-5). M-3 and M-5 receptors increase the excitability of neurons, whereas M-2 and M-4 receptors reduce the excitability. Because the scopolamine blocks all subtypes, the previous study did not identify which subtype contributes to the memory formation. By injecting several types of mAChR antagonists into the IMM, in this study we determined which mAChR subtype plays a critical role in imprinting. First, the effects of antagonists on the excitatory receptor subtypes M-3 and M-5 were examined. Injection of the M-3 antagonist (DAU5884) at 20 mM or the M-5 antagonist (ML381) at 2 mM impaired imprinting. Considering the pKi value of DAU5884, the impairment seems to be caused by DAU5884 binding to M-3 and/or M-4 receptors. Second, the effect of antagonists on the inhibitory receptor subtype M-2 was examined. The results showed that the M-2 antagonist (AQ-RA741) impaired imprinting at a concentration of 20 mM. Considering the pKi value of AQ-RA741, the impairment seems to be caused by AQ-RA741 binding to M-2 and/or M-4. The findings of this study suggests that the excitatory receptor subtypes M-3 and M-5 and the inhibitory receptor subtype M-2 and/or M-4 cooperate to achieve the appropriate balance of acetylcholine signaling to execute imprinting.