Delayed procedural learning in α7-nicotinic acetylcholine receptor knockout mice.
Delayed procedural learning in α7-nicotinic acetylcholine receptor knockout mice.
复制标题
α7-烟碱乙酰胆碱受体敲除小鼠的程序学习延迟。
DOI：
10.1111/j.1601-183x.2011.00711.x
复制
发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Geyer MA
中科院分区：
文献类型：
--
作者：
Young JW;Meves JM;Tarantino IS;Caldwell S;Geyer MA
α7-烟碱型乙酰胆碱受体（nAChR）是治疗精神分裂症的一个重要靶点。然而，关于这种受体在认知中的作用的证据一直缺乏，部分原因是合适的配体的可用性有限。先前已检查了α7-nAChR敲除（KO）小鼠的行为，但迄今为止，使用跨物种可翻译性测试进行的认知评估有限。在此，我们评估了α7-nAChR KO和野生型（WT）同窝小鼠在执行功能的注意定势转换任务、空间工作记忆广度容量的径向臂迷宫测试和短时记忆的新物体识别测试中的认知表现。这些突变体的奖励动机进行了评估，使用累进比率断点测试。此外，我们评估了探索行为和感觉运动门控的行为模式监测和前脉冲抑制，分别。α7-nAChR KO小鼠表现出正常的集合移位，但在多个范式中程序性学习（规则获得）受损。空间跨度能力、短期记忆、食物动机、探索和感觉运动门控均与WT同窝仔相当。这里提出的数据支持的概念，这种受体是重要的程序性学习，当环境中的模式变得清晰，规则是学习。结合先前在这些小鼠中观察到的注意力受损，这一发现表明，应在注意力和程序性学习的临床研究中检查激动剂治疗，也许与认知行为治疗相结合。
The α7-nicotinic acetylcholine receptor (nAChR) has long been a procognitive therapeutic target to treat schizophrenia. Evidence on the role of this receptor in cognition has been lacking, however, in part due to the limited availability of suitable ligands. The behavior of α7-nAChR knockout (KO) mice has been examined previously, but cognitive assessments using tests with cross-species translatability have been limited to date. Here, we assessed the cognitive performance of α7-nAChR KO and wild-type (WT) littermate mice in the attentional set-shifting task of executive functioning, the radial arm maze test of spatial working memory span capacity and the novel object recognition test of short-term memory. The reward motivation of these mutants was assessed using the progressive ratio breakpoint test. In addition, we assessed the exploratory behavior and sensorimotor gating using the behavioral pattern monitor and prepulse inhibition, respectively. α7-nAChR KO mice exhibited normal set-shifting, but impaired procedural learning (rule acquisition) in multiple paradigms. Spatial span capacity, short-term memory, motivation for food, exploration and sensorimotor gating were all comparable to WT littermates. The data presented here support the notion that this receptor is important for such procedural learning, when patterns in the environment become clear and a rule is learned. In combination with the impaired attention observed previously in these mice, this finding suggests that agonist treatments should be examined in clinical studies of attention and procedural learning, perhaps in combination with cognitive behavioral therapy.