Cording Katherine R, Tu Emilie M, Wang Hongli, Agopyan-Miu Alexander H C W, Bateup Helen S
Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States.
Department of Neuroscience, University of California, Berkeley, Berkeley, United States.
Elife. 2025 Jul 21;13:RP100162. doi: 10.7554/eLife.100162.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by two major diagnostic criteria - persistent deficits in social communication and interaction, and the presence of restricted, repetitive patterns of behavior (RRBs). Evidence from both human and animal model studies of ASD suggests that alteration of striatal circuits, which mediate motor learning, action selection, and habit formation, may contribute to the manifestation of RRBs. is a syndromic ASD risk gene, and loss of function of in mice is associated with RRBs. How the loss of impacts striatal neuron function is largely unknown. In this study, we utilized mice to test whether altered striatal neuron activity contributes to aberrant motor behaviors relevant to ASD. We find that mice exhibit enhanced cortical drive of direct pathway striatal projection neurons (dSPNs). This enhanced drive is due to increased intrinsic excitability of dSPNs, which make them more responsive to cortical inputs. We find that mice exhibit spontaneous repetitive behaviors, increased motor routine learning, perseveration, and cognitive inflexibility. Increased corticostriatal drive may therefore contribute to the acquisition of repetitive, inflexible behaviors in mice.
自闭症谱系障碍（ASD）是一种神经发育障碍，其特征有两个主要诊断标准——社交沟通和互动方面的持续性缺陷，以及存在受限的、重复的行为模式（RRBs）。来自人类和ASD动物模型研究的证据表明，介导运动学习、动作选择和习惯形成的纹状体回路改变可能导致RRBs的表现。[此处原文缺失一个基因名称]是一种综合征性ASD风险基因，小鼠中该基因功能丧失与RRBs有关。该基因功能丧失如何影响纹状体神经元功能在很大程度上尚不清楚。在本研究中，我们利用[此处原文缺失小鼠品系名称]小鼠来测试纹状体神经元活动改变是否导致与ASD相关的异常运动行为。我们发现[此处原文缺失小鼠品系名称]小鼠表现出直接通路纹状体投射神经元（dSPNs）的皮质驱动增强。这种增强的驱动是由于dSPNs内在兴奋性增加，这使得它们对皮质输入更敏感。我们发现[此处原文缺失小鼠品系名称]小鼠表现出自发性重复行为、运动常规学习增加、持续性行为以及认知灵活性降低。因此，皮质纹状体驱动增加可能导致[此处原文缺失小鼠品系名称]小鼠出现重复、不灵活行为。
