RELN (Reelin) is one of the genes implicated in neurodevelopmental psychiatric vulnerability. Patients with neurodevelopmental disorders can experience impairments in fine motor skills. While Reelin modulates synaptic function, whether Reelin haploinsufficiency affects activity-dependent cortical plasticity which supports development of skilled movement is unclear. Here, heterozygous Reeler mutant (HRM) and Dab1 floxed/ +; Emx1-Cre mice both displayed learning improvements measured by the reach-to-grasp task, but their performance levels of the forelimb motor skill were lower, compared with controls. The level of skilled motor performance was correlated with the area of cortical representations of the trained forelimb, examined after 10 days of training. Furthermore, we hypothesized that the genetic haploinsufficiency also alters changes that occur during the early phase of the training. Examined on day 3, the training induced synaptic modifications of the layer III cortical neurons in (wild-type) WT mice, which were contributed by synaptic potentiation and increase in spontaneous action-potential driven glutamatergic-transmission. On the other hand, the basal excitatory and inhibitory synaptic function were depressed, affected both by presynaptic and postsynaptic synaptic impairments in naive HRM; and thus, no further training-induced synaptic plasticity occurred in HRM. Lastly, examined after 3 days of training, the gene enrichment observed in trained WT mice was absent in trained HRM mice. The finding suggests the Reelin haploinsufficiency alters the skilled motor function; and we propose the suppression of gene enrichment, and synaptic abnormality led by the genetic insufficiency may contribute to impede the occurrence of activity-dependent cortical plasticity.

中文翻译：

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Reelin单倍体不足会影响熟练的运动表现，与抑制小鼠中的训练诱导基因富集，突触功能和活动相关的皮质可塑性有关。

RELN（Reelin）是与神经发育性精神病易感性有关的基因之一。神经发育障碍患者可能会出现精细运动技能受损的情况。虽然Reelin调节突触功能，但Reelin单倍体功能不足是否会影响依赖于活动的皮质可塑性，从而支持熟练运动的发展尚不清楚。在这里，杂合的Reeler突变体（HRM）和Dab1趋于稳定。Emx1-Cre小鼠均表现出通过触手可及的任务所获得的学习改善，但与对照组相比，其前肢运动技能的表现水平较低。训练10天后检查，熟练的运动表现水平与训练后的前肢的皮质表征区域相关。此外，我们假设遗传单倍体机能不全也会改变训练初期的变化。在第3天进行了检查，该训练在WT小鼠（野生型）中诱导了III层皮质神经元的突触修饰，这是由突触增强和自发动作电位驱动的谷氨酸能传递增加所致。另一方面，天真HRM的突触前和突触后损伤均受到基础兴奋性和抑制性突触功能的抑制。因此，HRM中没有进一步的训练诱发的突触可塑性发生。最后，在训练3天后进行检查，在训练后的WT小鼠中没有观察到基因富集。该发现提示Reelin单倍体功能不足会改变熟练的运动功能。