Striatal Circuits as a Common Node for Autism Pathophysiology.
Striatal Circuits as a Common Node for Autism Pathophysiology.
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纹状体回路是自闭症病理生理学的常见节点。
DOI：
10.3389/fnins.2016.00027
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发表时间：
2016
影响因子：
4.3
通讯作者：
Fuccillo MV
中科院分区：
文献类型：
--
作者：
Fuccillo MV
自闭症谱系障碍 (ASD) 的特点是两个看似无关的症状领域——社交互动缺陷和行为输出的限制性、重复模式。自闭症谱系障碍症状的多样性是否代表大脑网络的分布式功能障碍或特定神经回路内的异常尚不清楚。据推测，纹状体功能障碍是自闭症谱系障碍中重复运动行为的基础，神经学和脑成像研究也支持了这一假设。然而，随着我们对纹状体功能的认识扩展到包括行为灵活性、动机状态、目标导向学习和注意力的调节，我们考虑纹状体生理学的改变是否是介导一系列自闭症相关行为的中心节点，包括作为该疾病标志的社交和认知缺陷。本综述研究了自闭症谱系障碍（ASD）的多种遗传小鼠模型，以探讨纹状体回路异常是否构成自闭症相关行为发展的常见病理生理机制。尽管研究的遗传损伤存在异质性，但许多遗传自闭症谱系障碍模型显示纹状体回路的结构和功能发生改变，以及异常行为，包括重复梳理毛发、刻板的运动习惯、社交互动和决策缺陷。啮齿类动物的比较分析提供了一个独特的机会，利用不断增长的遗传关联数据来揭示典型的神经回路，其功能障碍直接导致自闭症谱系障碍症状学的各个方面。对此类回路的描述可以为理解自闭症谱系障碍复杂的遗传病因学提供组织原则，也可以提供新的治疗途径。此外，对行为调节纹状体机制的关注也可能有助于探索其他神经精神疾病的发病机制，这些疾病与自闭症谱系障碍表现出重叠的行为缺陷。
Autism spectrum disorders (ASD) are characterized by two seemingly unrelated symptom domains—deficits in social interactions and restrictive, repetitive patterns of behavioral output. Whether the diverse nature of ASD symptomatology represents distributed dysfunction of brain networks or abnormalities within specific neural circuits is unclear. Striatal dysfunction is postulated to underlie the repetitive motor behaviors seen in ASD, and neurological and brain-imaging studies have supported this assumption. However, as our appreciation of striatal function expands to include regulation of behavioral flexibility, motivational state, goal-directed learning, and attention, we consider whether alterations in striatal physiology are a central node mediating a range of autism-associated behaviors, including social and cognitive deficits that are hallmarks of the disease. This review investigates multiple genetic mouse models of ASD to explore whether abnormalities in striatal circuits constitute a common pathophysiological mechanism in the development of autism-related behaviors. Despite the heterogeneity of genetic insult investigated, numerous genetic ASD models display alterations in the structure and function of striatal circuits, as well as abnormal behaviors including repetitive grooming, stereotypic motor routines, deficits in social interaction and decision-making. Comparative analysis in rodents provides a unique opportunity to leverage growing genetic association data to reveal canonical neural circuits whose dysfunction directly contributes to discrete aspects of ASD symptomatology. The description of such circuits could provide both organizing principles for understanding the complex genetic etiology of ASD as well as novel treatment routes. Furthermore, this focus on striatal mechanisms of behavioral regulation may also prove useful for exploring the pathogenesis of other neuropsychiatric diseases, which display overlapping behavioral deficits with ASD.