Optogenetic-guided cortical plasticity after nerve injury
Optogenetic-guided cortical plasticity after nerve injury
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DOI：
10.1073/pnas.1100815108
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发表时间：
2011-05-24
影响因子：
11.1
通讯作者：
Pelled, Galit
中科院分区：
文献类型：
--
作者：
Li, Nan;Downey, John E.;Pelled, Galit
周围神经损伤引起感觉功能障碍，其被认为是由于损伤对侧和同侧的躯体感觉皮层中发生的神经元活动的变化。最近的研究表明，在剥夺初级体感皮层（S1）中观察到的扭曲的功能反应可能是抑制性中间神经元活动增加的结果，并通过transcallosa通路介导。本研究的目的是开发一种策略，操纵和控制transcallosa活动，以促进适当的可塑性，通过引导皮层重组在大鼠模型的感觉剥夺。由于transcallosal纤维主要来源于兴奋性锥体神经元胞体位于第三和第五层，在大鼠S1兴奋性神经元的工程表达盐视紫红质，光敏氯离子泵，触发神经元超极化。从电生理学，光学成像和功能性MRI测量的结果是一致的，在剥夺S1，活动响应于完整的前爪电刺激显着增加的同时照明的盐视紫红质在健康的S1。光遗传学操作有效地减少了剥夺皮层的不良抑制，并揭示了transcallosa的预测，显示半球间的神经可塑性，从而建立了基础，以制定改进的康复策略，以恢复皮层功能的主要贡献。
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 interneuron 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 interhemispheric neuroplasticity and thus, setting a foundation to develop improved rehabilitation strategies to restore cortical functions.