Synaptic and Genetic Bases of Impaired Motor Learning Associated with Modified Experience-Dependent Cortical Plasticity in Heterozygous <i>Reeler</i> Mutants
Synaptic and Genetic Bases of Impaired Motor Learning Associated with Modified Experience-Dependent Cortical Plasticity in Heterozygous <i>Reeler</i> Mutants
复制标题
杂合子 <i>Reeler</i> 突变体中与改进的经验依赖性皮质可塑性相关的运动学习受损的突触和遗传基础
DOI：
10.1093/cercor/bhab227
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Katsuyama Yu
中科院分区：
文献类型：
--
作者：
Nishibe Mariko;Toyoda Hiroki;Hiraga Shin-ichiro;Yamashita Toshihide;Katsuyama Yu
神经发育障碍患者表现出运动技能学习受损。目前尚不清楚遗传变异对突触功能和转录组谱的影响如何可能成为经验依赖性皮层可塑性的基础，这支持精细运动技能的发展。异源reelermutant（HRM）小鼠表现出的障碍，达到掌握学习，伴随着较广泛的皮质地图重组与野生型小鼠相比，10天的训练后，检查皮质内微刺激。通过3天的训练后的膜片钳记录评估，训练诱导的突触增强和增加的皮层第III层锥体神经元在野生型小鼠的突触传递。与此相反，基础兴奋性和抑制性突触功能被压抑，HRM小鼠突触前和突触后损伤的影响，因此，没有进一步的训练诱导的突触可塑性发生。HRM表现出下调皮质突触素，即刻早期基因表达，和基因富集，在3天的训练相比，训练野生型小鼠，显示使用定量逆转录聚合酶链反应，荧光化学，和RNA测序。我们证明，运动学习障碍与修改经验依赖性皮层可塑性至少部分归因于基础突触交替以及异常的早期经验诱导的基因富集HRM。
Patients with neurodevelopmental disorders show impaired motor skill learning. It is unclear how the effect of genetic variation on synaptic function and transcriptome profile may underlie experience-dependent cortical plasticity, which supports the development of fine motor skills.RELN(reelin) is one of the genes implicated in neurodevelopmental psychiatric vulnerability. Heterozygousreelermutant (HRM) mice displayed impairments in reach-to-grasp learning, accompanied by less extensive cortical map reorganization compared with wild-type mice, examined after 10 days of training by intracortical microstimulation. Assessed by patch-clamp recordings after 3 days of training, the training induced synaptic potentiation and increased glutamatergic-transmission of cortical layer III pyramidal neurons in wild-type mice. In contrast, the basal excitatory and inhibitory synaptic functions were depressed, affected both by presynaptic and postsynaptic impairments in HRM mice; and thus, no further training-induced synaptic plasticity occurred. HRM exhibited downregulations of cortical synaptophysin, immediate-early gene expressions, and gene enrichment, in response to 3 days of training compared with trained wild-type mice, shown using quantitative reverse transcription polymerase chain reaction, immunohistochemisty, and RNA-sequencing. We demonstrated that motor learning impairments associated with modified experience-dependent cortical plasticity are at least partially attributed by the basal synaptic alternation as well as the aberrant early experience-induced gene enrichment in HRM.