Developmental abnormality contributes to cortex-dependent motor impairments and higher intracortical current requirement in the reeler homozygous mutants
Developmental abnormality contributes to cortex-dependent motor impairments and higher intracortical current requirement in the reeler homozygous mutants
复制标题
发育异常导致 reeler 纯合突变体中皮质依赖性运动障碍和更高的皮质内电流需求
DOI：
10.1007/s00429-018-1647-8
复制
发表时间：
2018
影响因子：
3.1
通讯作者：
Yamashita Toshihide
中科院分区：
文献类型：
--
作者：
Nishibe Mariko;Katsuyama Yu;Yamashita Toshihide
这些减速突变体的运动缺陷在很大程度上被认为与小脑有关，而大脑皮层对减速运动行为的发育后果还没有得到检验。我们在这里表明，在需要前爪灵巧性的皮质依赖的双手任务中检查的模型中，存在加速突变的行为后果。使用皮质内微刺激，我们发现运动皮质的前肢代表显著减少。大脑皮层需要明显更高的电流来激发骨骼肌运动，这表明皮质跨突触的传播受到了干扰。当施加更大的电流时，发现速度运动表示被保存下来。为了阐明小脑萎缩和共济失调对结果的影响，用Reelin-Dab1信号缺陷局限于大脑皮层的失能-1(Dab1)CKO小鼠复制了快速小鼠的行为和神经生理学结果。在单粒到达和取回任务中，Dab1 CKO小鼠被进一步评估，显示成功取回的小球数量较少。这表明，局限于皮质的异常仍然降低了灵巧运动能力。虽然REELIN缺陷者可能存在肌肉功能障碍，但肌电图仪检查的前肢肌肉功能、神经肌肉接头的形态和胆碱乙酰转移酶的表达水平均正常。我们的结果表明，哺乳动物的板层结构对于前爪技能的表现和皮质输出中的跨突触效能是必要的。
The motor deficit of thereelermutants has largely been considered cerebellum related, and the developmental consequences of the cortex onreelermotor behavior have not been examined. We herein showed that there is a behavioral consequence toreelermutation in models examined at cortex-dependent bimanual tasks that require forepaw dexterity. Using intracortical microstimulation, we found the forelimb representation in the motor cortex was significantly reduced in thereeler. Thereelercortex required a significantly higher current to evoke skeletal muscle movements, suggesting the cortical trans-synaptic propagation is disrupted. When the higher current was applied, thereelermotor representation was found preserved. To elucidate the influence of cerebellum atrophy and ataxia on the obtained results, the behavioral and neurophysiological findings inreelermice were reproduced using the Disabled-1 (Dab1) cKO mice, in which the Reelin-Dab1 signal deficiency is confined to the cerebral cortex. The Dab1 cKO mice were further assessed at the single-pellet reach and retrieval task, displaying a lower number of successfully retrieved pellets. It suggests the abnormality confined to the cortex still reduced the dexterous motor performance. Although possible muscular dysfunction was reported inREELIN-deficient humans, the function of thereelerforelimb muscle examined by electromyography, morphology of neuromuscular junction and the expression level of choline acetyltransferase were normal. Our results suggest that the mammalian laminar structure is necessary for the forepaw skill performance and for trans-synaptic efficacy in the cortical output.