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使用改良的五选择序列反应时任务评估青少年小鼠的注意力控制。

Attentional Control in Adolescent Mice Assessed with a Modified Five Choice Serial Reaction Time Task.

机构信息

Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, via Morego, 30, 16163, Genova, Italy.

Department of Pharmacological and Pharmaceutical Science, University of Padova, Padova, Italy.

出版信息

Sci Rep. 2017 Aug 30;7(1):9936. doi: 10.1038/s41598-017-10112-8.

Abstract

Adolescence is a critical period for the development of higher-order cognitive functions. Unlike in humans, very limited tools are available to assess such cognitive abilities in adolescent rodents. We implemented a modified 5-Choice Serial Reaction Time Task (5CSRTT) to selectively measure attentiveness, impulsivity, broad monitoring, processing speed and distractibility in adolescent mice. 21-day old C57BL/6J mice reliably acquired this task with no sex-dependent differences in 10-12 days. A protocol previously used in adults was less effective to assess impulsiveness in adolescents, but revealed increased vulnerability in females. Next, we distinctively assessed selective, divided and broad monitoring attention modeling the human Spatial Attentional Resource Allocation Task (SARAT). Finally, we measured susceptibility to distractions using non-predictive cues that selectively disrupted attention. These paradigms were also applied to two genetically modified lines: the dopamine transporter (DAT) and catechol-O-methyltransferase (COMT) heterozygous. Adolescent DAT hypo-functioning mice showed attentional deficits and higher impulsivity as found in adults. In contrast to adults, adolescent COMT hypo-functioning mice showed decreased impulsivity and attentional resilience to distractors. These paradigms open new avenues to study the establishment of higher-order cognitive functions in mice, as well as an effective tool for drug-testing and genetic screenings focused on adolescence.

摘要

青春期是发展高阶认知功能的关键时期。与人类不同,评估青春期啮齿动物此类认知能力的工具非常有限。我们实施了改良的 5 选择连续反应时任务(5CSRTT),以选择性地测量青春期小鼠的注意力、冲动性、广泛监测、处理速度和分心。21 天大的 C57BL/6J 小鼠在 10-12 天内可靠地掌握了这项任务,没有性别差异。以前在成年人中使用的方案在评估青少年冲动性方面效果较差,但揭示了女性的脆弱性增加。接下来,我们通过模仿人类空间注意资源分配任务(SARAT),分别评估了选择性、分散性和广泛性监控注意力。最后,我们使用非预测线索测量了对分心的易感性,这些线索选择性地破坏了注意力。这些范式也应用于两种基因修饰系:多巴胺转运蛋白(DAT)和儿茶酚-O-甲基转移酶(COMT)杂合子。青春期 DAT 功能低下的小鼠表现出注意力缺陷和更高的冲动性,这与成年小鼠相同。与成年小鼠不同,青春期 COMT 功能低下的小鼠表现出冲动性降低和对分心物的注意力恢复力增强。这些范式为研究小鼠高阶认知功能的建立开辟了新途径,也是药物测试和针对青春期的基因筛选的有效工具。

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