Ryk controls remapping of motor cortex during functional recovery after spinal cord injury.

Ryk controls remapping of motor cortex during functional recovery after spinal cord injury.
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DOI:
10.1038/nn.4282
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发表时间:
2016-05
影响因子:
25
通讯作者:
Zou Y
Zou Y
中科院分区:
医学1区
文献类型:
--
作者:
Hollis ER 2nd;Ishiko N;Yu T;Lu CC;Haimovich A;Tolentino K;Richman A;Tury A;Wang SH;Pessian M;Jo E;Kolodkin A;Zou Y

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不完全性脊髓损伤后,通过康复可以实现有限的功能恢复。消除排斥性Wnt受体,Ryk的功能,无论是在运动皮层条件性敲除或单克隆抗体输注,导致增加皮质脊髓轴突侧支与突触前点在脊髓和增强恢复前肢达到和抓地力的功能后,颈椎背柱病变。使用光学刺激,我们观察到运动皮层输出地图经历了巨大的变化后,受伤和后肢皮质区被招募来控制前肢随着时间的推移。此外,在Ryk cKO中,更大的皮质区域专用于控制前肢。在没有每周特定任务训练的情况下,异位皮质区的募集大大减少,即使在Ryk cKO中也没有显著的功能恢复。我们的研究提供的证据表明,最大的电路重组和功能恢复可以通过结合分子操纵和特定任务的训练。
Limited functional recovery can be achieved with rehabilitation after incomplete spinal cord injury. Eliminating the function of a repulsive Wnt receptor, Ryk, by either conditional knockout in the motor cortex or monoclonal antibody infusion, resulted in increased corticospinal axon collateral branches with pre-synaptic puncta in the spinal cord and enhanced recovery of forelimb reaching and grasping function following a cervical dorsal column lesion. Using optical stimulation, we observed that motor cortical output maps underwent massive changes after injury and the hindlimb cortical areas were recruited to control the forelimb over time. Furthermore, a greater cortical area was dedicated to control the forelimb in Ryk cKO. In the absence of weekly task-specific training, recruitment of ectopic cortical areas was greatly reduced without significant functional recovery even in Ryk cKO. Our study provides evidence that maximal circuit reorganization and functional recovery can be achieved by combining molecular manipulation and task-specific training.