Mice Lacking M1 and M3 Muscarinic Acetylcholine Receptors Have Impaired Odor Discrimination and Learning.
Mice Lacking M1 and M3 Muscarinic Acetylcholine Receptors Have Impaired Odor Discrimination and Learning.
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DOI：
10.3389/fnsyn.2017.00004
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发表时间：
2017
影响因子：
3.7
通讯作者：
Araneda RC
中科院分区：
文献类型：
--
作者：
Chan W;Singh S;Keshav T;Dewan R;Eberly C;Maurer R;Nunez-Parra A;Araneda RC
胆碱能系统有广泛的投射到嗅球（OB），在那里它产生状态依赖性的感觉门控调节。以前的工作已经表明，毒蕈碱乙酰胆碱（ACh）受体（mAChRs）在调节OB神经元的兴奋性，特别是M1受体的突出作用。在这里，我们研究了M1和M3 mAChR亚型对嗅觉加工的贡献，使用这些受体基因缺失的小鼠，M1−/−和M1/M3−/−敲除（KO）小鼠。M1和M3 mAChRs的基因消融导致了密切相关分子（包括立体异构体）的气味辨别能力的显着不足。然而，不同分子、社会气味（例如，尿）和新物体识别不受影响。此外，KO小鼠在联想气味学习任务中表现出学习受损，学习以较慢的速度辨别气味，这表明短期和长期记忆都受到mAChR功能障碍的破坏。有趣的是，KO小鼠在年轻时表现出嗅觉神经发生减少，这在老年动物中没有维持。在老年动物中，嗅觉缺陷可以通过增加暴露于嗅觉丰富的环境后整合到OB中的新生神经元的数量来恢复，这表明毒蕈碱调节和成年神经发生可能是嗅觉系统用于改善嗅觉加工的两种不同机制。
The cholinergic system has extensive projections to the olfactory bulb (OB) where it produces a state-dependent regulation of sensory gating. Previous work has shown a prominent role of muscarinic acetylcholine (ACh) receptors (mAChRs) in regulating the excitability of OB neurons, in particular the M1 receptor. Here, we examined the contribution of M1 and M3 mAChR subtypes to olfactory processing using mice with a genetic deletion of these receptors, the M1−/− and the M1/M3−/− knockout (KO) mice. Genetic ablation of the M1 and M3 mAChRs resulted in a significant deficit in odor discrimination of closely related molecules, including stereoisomers. However, the discrimination of dissimilar molecules, social odors (e.g., urine) and novel object recognition was not affected. In addition the KO mice showed impaired learning in an associative odor-learning task, learning to discriminate odors at a slower rate, indicating that both short and long-term memory is disrupted by mAChR dysfunction. Interestingly, the KO mice exhibited decreased olfactory neurogenesis at younger ages, a deficit that was not maintained in older animals. In older animals, the olfactory deficit could be restored by increasing the number of new born neurons integrated into the OB after exposing them to an olfactory enriched environment, suggesting that muscarinic modulation and adult neurogenesis could be two different mechanism used by the olfactory system to improve olfactory processing.