Altered attentional processing in male and female rats in a prenatal valproic acid exposure model of autism spectrum disorder
Altered attentional processing in male and female rats in a prenatal valproic acid exposure model of autism spectrum disorder
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DOI：
10.1002/aur.1852
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发表时间：
2017-12-01
期刊：
影响因子：
4.7
通讯作者：
Laxmi, T. Rao
中科院分区：
文献类型：
--
作者：
Anshu, Kumari;Nair, Ajay Kumar;Laxmi, T. Rao
注意力是有效感知和最佳目标驱动行为的基础。完整的注意加工对于社交和沟通技能的发展至关重要。因此，注意力缺陷可能是自闭症谱系障碍（ASD）核心病理生理学的贡献者。ASD的临床证据提示注意力及其控制受损，但潜在的机制仍然难以捉摸。我们使用5-选择系列反应时间任务（5-CSRTT）在产前丙戊酸（VPA）ASD模型中检查了持续的空间分配注意力。与对照组相比，雄性和雌性VPA大鼠在5-CSRTT训练期间随着注意力需求的增加，准确率逐渐降低，遗漏率较高，并且在进行参数任务操作时表现出进一步的性能下降。值得注意的是，尽管VPA暴露会引起男女注意力缺陷，但存在特定于任务参数的性别差异。重要的是，我们没有在VPA大鼠中发现冲动或动机缺陷的证据，但我们确实发现了社会偏好降低，以及暗示前注意信息处理障碍的感觉运动缺陷。重要的是，有了固定的规则、分级的难度和更多的时间，VPA大鼠可以成功地接受注意力任务的训练。据我们所知，这是第一个研究VPA模型中的注意功能。我们的工作强调了在ASD动物模型中研究两性的必要性，并验证了VPA模型在寻求对异常注意力功能的机械理解和评估合适的治疗靶点方面的应用。Autism Res2017，10：1929-1944. (c)2017年国际自闭症研究学会，Wiley Periodicals，Inc.Lay SummaryWe研究了产前暴露于丙戊酸（VPA）的大鼠，这是一种已建立的自闭症啮齿动物模型。雄性和雌性VPA大鼠都有一系列具有性别特异性特征的注意力障碍。重要的是，有了固定的规则、分级的难度和更多的时间，VPA大鼠可以成功地接受注意力任务的训练。我们的工作验证了使用VPA模型在寻求评估合适的治疗目标，以改善注意力表现。
Attention is foundational to efficient perception and optimal goal driven behavior. Intact attentional processing is crucial for the development of social and communication skills. Deficits in attention are therefore likely contributors to the core pathophysiology of autism spectrum disorder (ASD). Clinical evidence in ASD is suggestive of impairments in attention and its control, but the underlying mechanisms remain elusive. We examined sustained, spatially divided attention in a prenatal valproic acid (VPA) model of ASD using the 5-choice serial reaction time task (5-CSRTT). As compared to controls, male and female VPA rats had progressively lower accuracy and higher omissions with increasing attentional demands during 5-CSRTT training, and showed further performance decrements when subjected to parametric task manipulations. It is noteworthy that although VPA exposure induced attentional deficits in both sexes, there were task parameter specific sex differences. Importantly, we did not find evidence of impulsivity or motivational deficits in VPA rats but we did find reduced social preference, as well as sensorimotor deficits that suggest pre-attentional information processing impairments. Importantly, with fixed rules, graded difficulty levels, and more time, VPA rats could be successfully trained on the attentional task. To the best of our knowledge, this is the first study examining attentional functions in a VPA model. Our work underscores the need for studying both sexes in ASD animal models and validates the use of the VPA model in the quest for mechanistic understanding of aberrant attentional functions and for evaluating suitable therapeutic targets. Autism Res2017, 10: 1929-1944. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.Lay SummaryWe studied rats prenatally exposed to valproic acid (VPA), an established rodent model of autism. Both male and female VPA rats had a range of attentional impairments with sex-specific characteristics. Importantly, with fixed rules, graded difficulty levels, and more time, VPA rats could be successfully trained on the attentional task. Our work validates the use of the VPA model in the quest for evaluating suitable therapeutic targets for improving attentional performance.