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Optogenetic-guided cortical plasticity after nerve injury

机译:神经损伤后光遗传学指导的皮质可塑性

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摘要

Peripheral nerve injury causes sensory dysfunctions that are thought to be attributable to changes in neuronal activity occurring in somatosensory cortices both contralateral and ipsilateral to the injury. Recent studies suggest that distorted functional response observed in deprived primary somatosensory cortex (S1) may be the result of an increase in inhibitory intemeuron activity and is mediated by the transcallosal pathway. The goal of this study was to develop a strategy to manipulate and control the transcallosal activity to facilitate appropriate plasticity by guiding the cortical reorganization in a rat model of sensory deprivation. Since transcallosal fibers originate mainly from excitatory pyramidal neurons somata situated in laminae III and V, the excitatory neurons in rat S1 were engineered to express halorhodopsin, a light-sensitive chloride pump that triggers neuronal hyperpolarization. Results from electrophysiology, optical imaging, and functional MRI measurements are concordant with that within the deprived S1, activity in response to intact forepaw electrical stimulation was significantly increased by concurrent illumination of halorhodopsin over the healthy S1. Optogenetic manipulations effectively decreased the adverse inhibition of deprived cortex and revealed the major contribution of the transcallosal projections, showing interhemi-spheric neuroplasticity and thus, setting a foundation to develop improved rehabilitation strategies to restore cortical functions.
机译:周围神经损伤引起感觉功能障碍,据认为可归因于伤害对侧和同侧的体感皮质中发生的神经元活动的变化。最近的研究表明,在剥夺的初级体感皮层(S1)中观察到的功能反应失真可能是抑制性中间神经元活性增加的结果,并且是由跨call途径介导的。这项研究的目的是开发一种策略,通过指导大鼠感觉剥夺模型中的皮质重组,来操纵和控制跨乳腺活动,以促进适当的可塑性。由于跨call肌纤维主要来源于位于III和V层的兴奋性锥体神经细胞索马特,因此将大鼠S1中的兴奋性神经元改造为表达卤代视紫红质,这是一种光敏的氯化物泵,可触发神经元超极化。电生理,光学成像和功能性MRI测量的结果与被剥夺的S1内的结果一致,通过同时照射健康S1上的卤素视紫红质,显着提高了对完整前爪电刺激的响应活性。光遗传学操作有效地减少了剥夺皮层的不利抑制,并揭示了经call突投射的主要作用,显示了半球间神经可塑性,因此,为开发改进的康复策略以恢复皮层功能奠定了基础。

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  • 作者单位

    F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205 Department of Biomedical Engineering and , Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205;

    The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 Cellular Imaging Section, Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205 The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 Cellular Imaging Section, Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 Cellular Imaging Section, Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 Cellular Imaging Section, Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205 The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287;

    F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205 The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287;

    Department of Biomedical Engineering and , Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205 The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    recovery; amputation;

    机译:恢复;截肢;

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