Impaired auditory discrimination learning following perinatal nicotine exposure or β2 nicotinic acetylcholine receptor subunit deletion
Impaired auditory discrimination learning following perinatal nicotine exposure or β2 nicotinic acetylcholine receptor subunit deletion
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DOI：
10.1016/j.bbr.2012.03.002
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发表时间：
2012-05-16
影响因子：
2.7
通讯作者：
Picciotto, Marina R.
中科院分区：
文献类型：
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作者：
Horst, Nicole K.;Heath, Christopher J.;Picciotto, Marina R.
母亲在怀孕期间吸烟会损害暴露的后代在需要听觉刺激处理和感知的任务中的表现；然而，造成这些影响的烟草成分和潜在的神经生物学机制仍然不确定。在这项研究中，我们表明，在小鼠围产期发育过程中给予尼古丁会损害暴露的动物成熟后听觉辨别范式的表现。这表明尼古丁通过在发育早期表达的烟碱乙酰胆碱受体（nAChR）破坏听觉通路。我们还确定，缺乏含有 β 2 亚基（β 2* nAChR）的 nAChR 的小鼠在此任务中表现出类似的性能受损，这表明 β 2* nAChR 对于正常听觉辨别是必需的，或者说 β 2* nAChR 在任务执行所需电路的发育中发挥着关键作用。相比之下，围产期尼古丁暴露或β2亚基敲除对低速率任务的差异强化的获得和表现没有影响。这表明听觉辨别障碍不是学习和记忆普遍缺陷的结果，而可能是接触尼古丁和基因敲除动物的听觉刺激处理受损的结果。 (c) 2012 Elsevier B.V. 保留所有权利。
Maternal smoking during pregnancy can impair performance of the exposed offspring in tasks that require auditory stimulus processing and perception; however, the tobacco component(s) responsible for these effects and the underlying neurobiological mechanisms remain uncertain. In this study, we show that administration of nicotine during mouse perinatal development can impair performance in an auditory discrimination paradigm when the exposed animals are mature. This suggests that nicotine disrupts auditory pathways via nicotinic acetylcholine receptors (nAChRs) that are expressed at an early stage of development. We have also determined that mice which lack nAChRs containing the beta 2 subunit (beta 2* nAChRs) exhibit similarly compromised performance in this task, suggesting that beta 2* nAChRs are necessary for normal auditory discrimination or that beta 2* nAChRs play a critical role in development of the circuitry required for task performance. In contrast, no effect of perinatal nicotine exposure or beta 2 subunit knockout was found on the acquisition and performance of a differential reinforcement of low rate task. This suggests that the auditory discrimination impairments are not a consequence of a general deficit in learning and memory, but may be the result of compromised auditory stimulus processing in the nicotine-exposed and knockout animals. (c) 2012 Elsevier B.V. All rights reserved.