Altered motor learning and coordination in mouse models of autism spectrum disorder.
Altered motor learning and coordination in mouse models of autism spectrum disorder.
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DOI：
10.3389/fncel.2023.1270489
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发表时间：
2023
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
自闭症谱系障碍(ASD)是一种发病率越来越高的复杂神经发育障碍。目前已有超过1,000个风险基因与ASD有关，这表明病因不同。然而，该病的诊断标准仍然包括两个主要的行为领域--社交沟通和互动方面的缺陷，以及限制性和重复行为模式(RRB)的存在。与ASD相关的RRB既包括刻板印象的重复运动，也包括其他运动表现，包括步态、平衡、协调和运动技能学习的变化。近年来，由于纹状体在动作选择、运动学习和习惯形成中的作用，纹状体作为基底神经节的主要输入中心，被认为参与了这些与ASD相关的运动行为。许多ASD风险基因突变的小鼠模型已经被开发出来，并被证明在ASD相关行为中发生了变化。一种常用的测试，加速旋转棒，允许评估基本的运动协调和运动技能学习。在这个依赖皮质纹状体的任务中，小鼠走在旋转的杆子上，逐渐加快速度。在这项任务的扩展版本中，小鼠利用纹状体依赖的学习机制来优化它们的运动程序，并在杆上停留更长时间。该综述总结了在一系列ASD小鼠模型上检测旋转棒性能的研究结果，以及由此产生的纹状体回路参与ASD相关运动行为的含义。虽然在这项任务中的表现在不同的鼠标模型中并不是一致的，但有一组模型显示出旋转机器人性能的提高。越来越多的研究表明，这种学习固定运动规律的倾向的增加可能反映了带有ASD风险基因突变的一组小鼠的皮质纹状体驱动力普遍增强。
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with increasing prevalence. Over 1,000 risk genes have now been implicated in ASD, suggesting diverse etiology. However, the diagnostic criteria for the disorder still comprise two major behavioral domains - deficits in social communication and interaction, and the presence of restricted and repetitive patterns of behavior (RRBs). The RRBs associated with ASD include both stereotyped repetitive movements and other motor manifestations including changes in gait, balance, coordination, and motor skill learning. In recent years, the striatum, the primary input center of the basal ganglia, has been implicated in these ASD-associated motor behaviors, due to the striatum’s role in action selection, motor learning, and habit formation. Numerous mouse models with mutations in ASD risk genes have been developed and shown to have alterations in ASD-relevant behaviors. One commonly used assay, the accelerating rotarod, allows for assessment of both basic motor coordination and motor skill learning. In this corticostriatal-dependent task, mice walk on a rotating rod that gradually increases in speed. In the extended version of this task, mice engage striatal-dependent learning mechanisms to optimize their motor routine and stay on the rod for longer periods. This review summarizes the findings of studies examining rotarod performance across a range of ASD mouse models, and the resulting implications for the involvement of striatal circuits in ASD-related motor behaviors. While performance in this task is not uniform across mouse models, there is a cohort of models that show increased rotarod performance. A growing number of studies suggest that this increased propensity to learn a fixed motor routine may reflect a common enhancement of corticostriatal drive across a subset of mice with mutations in ASD-risk genes.
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DOI：
10.1523/jneurosci.0925-21.2021
发表时间：
2021-10-20
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Berg EL;Jami SA;Petkova SP;Berz A;Fenton TA;Lerch JP;Segal DJ;Gray JA;Ellegood J;Wöhr M;Silverman JL
通讯作者：
Silverman JL
影响因子：
11.2
作者：
Beeler, Jeff A.;Cao, Zhen Fang Huang;Kheirbek, Mazen A.;Ding, Yunmin;Koranda, Jessica;Murakami, Mari;Kang, Un Jung;Zhuang, Xiaoxi
通讯作者：
Zhuang, Xiaoxi
影响因子：
4.7
作者：
Caldwell-Harris CL
通讯作者：
Caldwell-Harris CL
影响因子：
3.4
作者：
Belin, D.;Deroche-Gamonet, V.;Jaber, M.
通讯作者：
Jaber, M.
影响因子：
64.8
作者：
Barnes, TD;Kubota, Y;Graybiel, AM
通讯作者：
Graybiel, AM