Skilled Movements Require Non-apoptotic Bax/Bak Pathway-Mediated Corticospinal Circuit Reorganization.

Skilled Movements Require Non-apoptotic Bax/Bak Pathway-Mediated Corticospinal Circuit Reorganization.
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DOI:
10.1016/j.neuron.2017.04.019
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发表时间:
2017-05-03
期刊:
影响因子:
16.2
通讯作者:
Yoshida Y
Yoshida Y
中科院分区:
医学1区
文献类型:
--
作者:
Gu Z;Serradj N;Ueno M;Liang M;Li J;Baccei ML;Martin JH;Yoshida Y

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出生后早期的哺乳动物,包括人类婴儿,只能执行基本的运动任务。熟练行为的获得发生在以后,需要神经回路的解剖学变化来支持功能相关肌肉群的协调激活或抑制的发展。这种电路重组如何发生在出生后的发展仍然知之甚少。在这里,我们探讨了小鼠运动皮层和肌肉中皮质脊髓(CS)神经元之间的连接。使用跨突触病毒和电生理检测,我们确定了早期出生后重组的CS电路拮抗肌对。我们进一步表明,这种突触重排需要活性依赖性,非凋亡Bax/Bak-caspase信号级联反应。成年Bax/巴克突变小鼠表现出异常的拮抗肌对共激活和熟练的抓握缺陷,但正常的达到和检索行为。我们的研究结果揭示了驱动出生后运动回路重组的关键细胞和分子机制,以及对肌肉激活模式和熟练动作执行的影响。
Early postnatal mammals, including human babies, can perform only basic motor tasks. The acquisition of skilled behaviors occurs later, requiring anatomical changes in neural circuitry to support the development of coordinated activation or suppression of functionally related muscle groups. How this circuit reorganization occurs during postnatal development remains poorly understood. Here we explore the connectivity between corticospinal (CS) neurons in the motor cortex and muscles in mice. Using trans-synaptic viral and electrophysiological assays, we identify the early postnatal reorganization of CS circuitry for antagonistic muscle pairs. We further show that this synaptic rearrangement requires the activity-dependent, non-apoptotic Bax/Bak-caspase signaling cascade. Adult Bax/Bak mutant mice exhibit aberrant co-activation of antagonistic muscle pairs and skilled grasping deficits but normal reaching and retrieval behaviors. Our findings reveal key cellular and molecular mechanisms driving postnatal motor circuit reorganization and the resulting impacts on muscle activation patterns and the execution of skilled movements.
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