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J Neurosci:揭示控制个体随意运动的大脑神经回路

来源:生物谷 2014-05-10 15:47

2014年5月10日 讯 /生物谷BIOON/ --从大脑到脊髓传递信号的复杂回路控制着个体的随意运动,近日,来自索菲·戴维斯学院的研究者通过研究鉴别出了一种新型的控制回路,但是研究者缺少在神经水平上对其进行分析的工具,相关研究刊登于国际杂志the Journal of Neuroscience上。

研究者John Martin教授表示,我们利用了一种新型敏感遗传学技术消除了大脑皮层中的特殊基因从而改变了大脑的回路;皮层脊髓束对于随意运动非常重要,在遗传完整的小鼠机体中,皮层脊髓束信号可以从大脑皮层的一侧传递到脊髓的相反一侧,这样小鼠只会在某一侧手臂产生反应而不是两只手臂都有反应。

文章中研究者利用特殊的小鼠,比如敲除小鼠,其机体中的EphA4基因是从大脑皮层中移除的,这样的小鼠就会达到两只前肢产生反应,由于遗传操作可以改变小鼠大脑的神经回路,因此其会引发信号从大脑皮层一侧传递到脊髓另一侧;当前比较棘手的问题就是揭示随意运动过程中大脑的功能发挥的机制,揭示随意运动大脑回路的功能将帮助研究人员理解脑瘫的发生。

相关研究由国家神经疾病和中风研究所提供资助,本文研究为研究者揭示随意运动过程中大脑和脊髓的回路提供了一定思路,利用遗传工具,研究者希望未来将会对皮层脊髓束运动回路的连接和功能进行研究,用以恢复个体大脑或脊髓受损后的运动恢复。(生物谷Bioon.com)

 

EphA4-Mediated Ipsilateral Corticospinal Tract Misprojections Are Necessary for Bilateral Voluntary Movements But Not Bilateral Stereotypic Locomotion

Najet Serradj1, Sónia Paixão2, Tomasz Sobocki1, Mitchell Feinberg1, Rüdiger Klein2,3, Klas Kullander4, and John H. Martin1

 

In this study, we took advantage of the reported role of EphA4 in determining the contralateral spinal projection of the corticospinal tract (CST) to investigate the effects of ipsilateral misprojections on voluntary movements and stereotypic locomotion. Null EphA4 mutations produce robust ipsilateral CST misprojections, resulting in bilateral corticospinal tracts. We hypothesize that a unilateral voluntary limb movement, not a stereotypic locomotor movement, will become a bilateral movement in EphA4 knock-out mice with a bilateral CST. However, in EphA4 full knock-outs, spinal interneurons also develop bilateral misprojections. Aberrant bilateral spinal circuits could thus transform unilateral corticospinal control signals into bilateral movements. We therefore studied mice with conditional forebrain deletion of the EphA4 gene under control by Emx1, a gene expressed in the forebrain that affects the developing CST but spares brainstem motor pathways and spinal motor circuits. We examined two conditional knock-outs targeting forebrain EphA4 during performance of stereotypic locomotion and voluntary movement: adaptive locomotion over obstacles and exploratory reaching. We found that the conditional knock-outs used alternate stepping, not hopping, during overground locomotion, suggesting normal central pattern generator function and supporting our hypothesis of minimal CST involvement in the moment-to-moment control of stereotypic locomotion. In contrast, the conditional knock-outs showed bilateral voluntary movements under conditions when single limb movements are normally produced and, as a basis for this aberrant control, developed a bilateral motor map in motor cortex that is driven by the aberrant ipsilateral CST misprojections. Therefore, a specific change in CST connectivity is associated with and explains a change in voluntary movement.

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