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经颅脉冲磁场刺激促进异常神经回路的重组,纠正行为缺陷,而不会破坏正常的连接。

Transcranial pulsed magnetic field stimulation facilitates reorganization of abnormal neural circuits and corrects behavioral deficits without disrupting normal connectivity.

机构信息

Experimental and Regenerative Neuroscience, School of Animal Biology M317, The University of Western Australia, Crawley, WA 6009, Australia.

出版信息

FASEB J. 2012 Apr;26(4):1593-606. doi: 10.1096/fj.11-194878. Epub 2012 Jan 5.

Abstract

Although the organization of neuronal circuitry is shaped by activity patterns, the capacity to modify and/or optimize the structure and function of whole projection pathways using external stimuli is poorly defined. We investigate whether neuronal activity induced by pulsed magnetic fields (PMFs) alters brain structure and function. We delivered low-intensity PMFs to the posterior cranium of awake, unrestrained mice (wild-type and ephrin-A2A5(-/-)) that have disorganized retinocollicular circuitry and associated visuomotor deficits. Control groups of each genotype received sham stimulation. Following daily stimulation for 14 d, we measured biochemical, structural (anterograde tracing), and functional (electrophysiology and behavior) changes in the retinocollicular projection. PMFs induced BDNF, GABA, and nNOS expression in the superior colliculus and retina of wild-type and ephrin-A2A5(-/-) mice. Furthermore, in ephrin-A2A5(-/-) mice, PMFs corrected abnormal neuronal responses and selectively removed inaccurate ectopic axon terminals to improve structural and functional organization of their retinocollicular projection and restore normal visual tracking behavior. In contrast, PMFs did not alter the structure or function of the normal projection in wild-type mice. Sham PMF stimulation had no effect on any mice. Thus, PMF-induced biochemical changes are congruent with its capacity to facilitate beneficial reorganization of abnormal neural circuits without disrupting normal connectivity and function.

摘要

虽然神经元回路的组织受活动模式的影响,但利用外部刺激来改变和/或优化整个投射通路的结构和功能的能力还未被充分定义。我们研究了脉冲磁场(PMFs)诱导的神经元活动是否会改变大脑结构和功能。我们将低强度的 PMFs 施加到清醒、不受约束的小鼠(野生型和 Ephrin-A2A5(-/-))的后颅顶,这些小鼠的视网膜-丘系回路紊乱,伴有视觉运动缺陷。每个基因型的对照组都接受了假刺激。在每日刺激 14 天后,我们测量了视网膜-丘系投射的生化、结构(顺行示踪)和功能(电生理学和行为)变化。PMFs 诱导了野生型和 Ephrin-A2A5(-/-)小鼠的上丘和视网膜中的 BDNF、GABA 和 nNOS 表达。此外,在 Ephrin-A2A5(-/-)小鼠中,PMFs 纠正了异常的神经元反应,并选择性地去除了不准确的异位轴突末梢,从而改善了其视网膜-丘系投射的结构和功能组织,并恢复了正常的视觉跟踪行为。相比之下,PMFs 并没有改变野生型小鼠正常投射的结构或功能。假 PMF 刺激对任何小鼠都没有影响。因此,PMF 诱导的生化变化与其促进异常神经回路有益重组的能力一致,而不会破坏正常的连接和功能。

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