Pappas Samuel S, Leventhal Daniel K, Albin Roger L, Dauer William T
Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA; Michigan Alzheimer Disease Center, University of Michigan, Ann Arbor, Michigan, USA; Geriatrics Research, Education, and Clinical Center, VAAAHS, Ann Arbor, Michigan, USA.
Curr Top Dev Biol. 2014;109:97-169. doi: 10.1016/B978-0-12-397920-9.00001-9.
This chapter focuses on neurodevelopmental diseases that are tightly linked to abnormal function of the striatum and connected structures. We begin with an overview of three representative diseases in which striatal dysfunction plays a key role--Tourette syndrome and obsessive-compulsive disorder, Rett's syndrome, and primary dystonia. These diseases highlight distinct etiologies that disrupt striatal integrity and function during development, and showcase the varied clinical manifestations of striatal dysfunction. We then review striatal organization and function, including evidence for striatal roles in online motor control/action selection, reinforcement learning, habit formation, and action sequencing. A key barrier to progress has been the relative lack of animal models of these diseases, though recently there has been considerable progress. We review these efforts, including their relative merits providing insight into disease pathogenesis, disease symptomatology, and basal ganglia function.
本章聚焦于与纹状体及相关结构功能异常紧密相关的神经发育疾病。我们首先概述三种以纹状体功能障碍为关键因素的代表性疾病——妥瑞氏症和强迫症、雷特综合征以及原发性肌张力障碍。这些疾病凸显了在发育过程中破坏纹状体完整性和功能的不同病因,并展示了纹状体功能障碍的多样临床表现。然后,我们回顾纹状体的组织和功能,包括纹状体在在线运动控制/动作选择、强化学习、习惯形成和动作序列方面所起作用的证据。尽管最近取得了显著进展,但这些疾病的动物模型相对匮乏仍是阻碍研究进展的一个关键因素。我们回顾这些研究成果,包括它们在深入了解疾病发病机制、疾病症状学和基底神经节功能方面的相对优势。