Deficits of synaptic functions in hippocampal slices prepared from aged mice null alpha 7 nicotinic acetylcholine receptors
Deficits of synaptic functions in hippocampal slices prepared from aged mice null alpha 7 nicotinic acetylcholine receptors
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α7 烟碱乙酰胆碱受体缺失的老年小鼠海马切片突触功能缺陷
DOI：
10.1016/j.neulet.2014.04.018
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发表时间：
2014
影响因子：
2.5
通讯作者：
Wu Jie
中科院分区：
文献类型：
--
作者：
Ma Luyao;Turner Dharshaun;Zhang Junfang;Wang Qingwen;Wang Michele;Shen Jianxing;Zhang Shijiang;Wu Jie
α7(α7)烟碱型乙酰胆碱受体(α7-nAChR)是脑内高表达的nAChR亚型之一。NAChRs的激活增强了动物的认知、学习和记忆能力。然而，α7-nAChRs的基因敲除(KO)在动物认知相关行为中的作用仍不清楚。早期的一份报告显示，α7-nAChR KO小鼠没有表现出行为表型，这与α7-nAChRs在正常的认知相关行为中的作用有关。后来，α7-nAChR KO小鼠被发现在动物空间辨别能力上存在缺陷。α7-nAChRs在衰老过程中海马区突触功能改变中的作用目前尚不清楚。在这里，我们通过使用场电位记录在成年(12-14月龄)和老年(22-24月龄)α7-nAChR KO和年龄匹配的野生型(WT)小鼠的海马片标本中检测突触功能来解决这个问题。我们发现，与老年WT小鼠相比，老年α7-nAChR KO小鼠的诱发场突触电位显著减小，海马CA3CA1突触的长时程增强(LTP)受损。然而，成年α7-nAChR KO小鼠并没有表现出明显的LTP缺陷，尽管与成年WT小鼠相比，基本的突触传递也减少了。在两个年龄组中，α7-nAChR KO和WT小鼠的成对脉冲促进作用没有显著差异。综上所述，本研究首次提供了直接证据，证明老年α7-nAChR KO小鼠存在突触功能受损，表明α7-nAChRs在衰老过程中维持认知功能方面的重要性。
Alpha 7 (α7) nicotinic acetylcholine receptor (α7-nAChR) is one of most high expressed nAChR subtypes in the brain. The activation of nAChRs enhances animal cognitive, learning and memory abilities. However, the role of genetic knockout (KO) of α7-nAChRs in animal cognition-associated behaviors is still obscure. An early report showed that α7-nAChR KO mice did not exhibit behavioral phenotypes, concerning the roles of α7-nAChRs in normal, cognition-associated behaviors. Later, α7-nAChR KO mice were found a deficit in animal spatial discrimination. The roles of α7-nAChRs in the alterations of hippocampal synaptic function during aging process are largely unknown. Here, we address this question by examining synaptic function using field potential recording in hippocampal slice preparations from adult (12–14 months old) and aged (22–24 months old) α7-nAChR KO and age-matched wild-type (WT) mice. We found that compared to aged WT mice, aged α7-nAChR KO mice exhibited significantly reduced size of evoked field synaptic potential and impaired long-term potentiation (LTP) in hippocampal CA3-CA1 synapses. However, adult α7-nAChR KO mice did not show a clear deficit in LTP although the basic synaptic transmission was also reduced compared to adult WT mice. In both age groups, there was no significant difference of paired-pulse facilitation between α7-nAChR KO and WT mice. Collectively, this study provides direct evidence, for the first time, that the impaired synaptic function occurs in aged α7-nAChR KO mice, suggesting an importance of α7-nAChRs in maintaining cognitive function during aging process.