Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University of California-Irvine, 356A Med Surge II, Irvine, CA, 92697-4625, USA.
UC Irvine Center for the Neurobiology of Learning and Memory, University of California-Irvine, Irvine, CA, 92697, USA.
Mol Neurobiol. 2023 Feb;60(2):545-565. doi: 10.1007/s12035-022-03095-9. Epub 2022 Nov 2.
Almost all brain cells contain cilia, antennae-like microtubule-based organelles. Yet, the significance of cilia, once considered vestigial organelles, in the higher-order brain functions is unknown. Cilia act as a hub that senses and transduces environmental sensory stimuli to generate an appropriate cellular response. Similarly, the striatum, a brain structure enriched in cilia, functions as a hub that receives and integrates various types of environmental information to drive appropriate motor response. To understand cilia's role in the striatum functions, we used loxP/Cre technology to ablate cilia from the dorsal striatum of male mice and monitored the behavioral consequences. Our results revealed an essential role for striatal cilia in the acquisition and brief storage of information, including learning new motor skills, but not in long-term consolidation of information or maintaining habitual/learned motor skills. A fundamental aspect of all disrupted functions was the "time perception/judgment deficit." Furthermore, the observed behavioral deficits form a cluster pertaining to clinical manifestations overlapping across psychiatric disorders that involve the striatum functions and are known to exhibit timing deficits. Thus, striatal cilia may act as a calibrator of the timing functions of the basal ganglia-cortical circuit by maintaining proper timing perception. Our findings suggest that dysfunctional cilia may contribute to the pathophysiology of neuro-psychiatric disorders, as related to deficits in timing perception.
几乎所有的脑细胞都含有纤毛,这是一种类似天线的微管细胞器。然而,纤毛在大脑高级功能中的意义尚不清楚,它们曾经被认为是退化的细胞器。纤毛作为一个枢纽,能够感知和转导环境感觉刺激,从而产生适当的细胞反应。同样,纹状体是一种富含纤毛的大脑结构,它作为一个枢纽,接收和整合各种类型的环境信息,以驱动适当的运动反应。为了了解纤毛在纹状体功能中的作用,我们使用 loxP/Cre 技术从雄性小鼠的背侧纹状体中剔除纤毛,并监测其行为后果。我们的结果表明,纹状体纤毛在信息的获取和短暂存储中起着至关重要的作用,包括学习新的运动技能,但在信息的长期巩固或维持习惯性/习得的运动技能方面没有作用。所有受干扰功能的一个基本方面是“时间感知/判断缺陷”。此外,观察到的行为缺陷形成了一个集群,涉及到涉及纹状体功能的重叠的精神障碍的临床表现,这些临床表现已知存在时间缺陷。因此,纹状体纤毛可以通过维持适当的时间感知来充当基底神经节-皮质回路的定时功能的校准器。我们的发现表明,功能失调的纤毛可能导致与时间感知缺陷相关的神经精神障碍的病理生理学。