小柯机器人

加拿大渥太华大学Simon X. Chen课题组发现，蓝斑核激活可挽救16p11.2缺失自闭症小鼠模型中的延迟运动学习。这一研究成果于2021年3月22日在线发表在国际学术期刊《自然—神经科学》上。

研究人员发现，具有染色体16p11.2同义缺失（与自闭症谱系障碍相关的常见拷贝数变异）的小鼠也表现出延迟的运动学习，而没有表现出明显的运动缺陷。使用处于清醒状态的小鼠体内的双光子成像，研究人员发现，成年雄性16p11.2缺失小鼠的运动皮质中第2/3层兴奋性神经元在学习的初始阶段表现出异常高的活性，并且在学习过程中-导致脊柱重组延长。

蓝斑核去甲肾上腺素能神经元的药理学激活足以挽救这些小鼠的回路缺陷和延迟的运动学习。这些研究结果揭示了去甲肾上腺素能神经调节在改善16p11.2缺失雄性小鼠延迟运动学习中的作用。

据介绍，自闭症谱系障碍儿童通常在实现运动发育关键点（如爬行、走路和言语清晰度）方面表现出延迟。然而，关于运动相关缺陷的神经机制知之甚少。

附：英文原文

Title: Delayed motor learning in a 16p11.2 deletion mouse model of autism is rescued by locus coeruleus activation

Author: Xuming Yin, Nathaniel Jones, Jungwoo Yang, Nabil Asraoui, Marie-Eve Mathieu, Liwen Cai, Simon X. Chen

Issue&Volume: 2021-03-22

Abstract: Children with autism spectrum disorder often exhibit delays in achieving motor developmental milestones such as crawling, walking and speech articulation. However, little is known about the neural mechanisms underlying motor-related deficits. Here, we reveal that mice with a syntenic deletion of the chromosome 16p11.2, a common copy number variation associated with autism spectrum disorder, also exhibit delayed motor learning without showing gross motor deficits. Using in vivo two-photon imaging in awake mice, we find that layer 2/3 excitatory neurons in the motor cortex of adult male 16p11.2-deletion mice show abnormally high activity during the initial phase of learning, and the process of learning-induced spine reorganization is prolonged. Pharmacogenetic activation of locus coeruleus noradrenergic neurons was sufficient to rescue the circuit deficits and the delayed motor learning in these mice. Our results unveil an unanticipated role of noradrenergic neuromodulation in improving the delayed motor learning in 16p11.2-deletion male mice. Yin et al. show that motor learning is delayed in mice with 16p11.2 deletion, associated with abnormal ensemble activity and delayed spine remodeling in motor cortex and reduced activity of of locus coeruleus noradrenergic neurons. The motor-related abnormalities were rescued by activation of ocus coeruleus noradrenergic neurons.

DOI: 10.1038/s41593-021-00815-7

Source: https://www.nature.com/articles/s41593-021-00815-7

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex