Multiple genetic factors related to autism spectrum disorder (ASD) have been identified, but the biological mechanisms remain obscure. Timothy syndrome (TS), associated with syndromic ASD, is caused by a gain‐of‐function mutation, G406R, in the pore‐forming subunit of L‐type Ca²⁺ channels, Ca_v1.2. In this study, a mouse model of TS, TS2‐neo, was used to enhance behavioral phenotyping and to identify developmental anomalies in inhibitory neurons. Using the IntelliCage, which enables sequential behavioral tasks without human handling and mouse isolation stress, high social competitive dominance was observed in TS2‐neo mice. Furthermore, histological analysis demonstrated inhibitory neuronal abnormalities in the neocortex, including an excess of smaller‐sized inhibitory presynaptic terminals in the somatosensory cortex of young adolescent mice and higher numbers of migrating inhibitory neurons from the medial ganglionic eminence during embryonic development. In contrast, no obvious changes in excitatory synaptic terminals were found. These novel neural abnormalities in inhibitory neurons of TS2‐neo mice may result in a disturbed excitatory/inhibitory (E/I) balance, a key feature underlying ASD.

中文翻译：

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Timothy 综合征的小鼠模型表现出改变的社会竞争优势和抑制性神经元发育。

已经确定了与自闭症谱系障碍 (ASD) 相关的多种遗传因素，但生物学机制仍不清楚。Timothy 综合征 (TS) 与综合征性 ASD 相关，由 L 型 Ca ²⁺通道的成孔亚基Ca _v中的功能获得性突变 G406R 引起1.2. 在这项研究中，TS 小鼠模型 TS2-neo 用于增强行为表型并识别抑制性神经元的发育异常。使用 IntelliCage，它可以在没有人工操作和小鼠隔离压力的情况下实现连续的行为任务，在 TS2-neo 小鼠中观察到了高度的社会竞争优势。此外，组织学分析表明，新皮层中存在抑制性神经元异常，包括幼鼠体感皮层中体积较小的抑制性突触前末梢过多，以及在胚胎发育过程中从内侧神经节隆起处迁移的抑制性神经元数量较多。相比之下，兴奋性突触末梢没有明显变化。