Neural Mechanisms of Compensating for Brain Damage

描述（由研究者提供）：最可靠的结果之一 存活的脑损伤是动物经历了主要的行为变化， 他们试图弥补他们的缺陷。知道这些行为 与损伤引起的大脑变化相互作用的变化可能对 了解大脑损伤的神经和行为适应。本研究 将调查发生在一个人身上的部分去神经的可能性， 局部皮层损伤后的连接区域促进某些类型的学习 以及这种学习背后的神经元变化。老鼠的能力， 感觉运动皮层（SMC）前肢区域的单侧损伤， 用未受损的前肢获得熟练的运动任务最近被 发现与其完整的对应物相比有所增强。是 假设运动学习的增强是因为轻度的 病变引起的退行性事件促进了神经元的变化， 这种学习发生在损伤的相对的初级运动皮层。因为这些 损伤导致大鼠依赖于这条肢体，这提供了一个独特的模型， 系统研究神经机制的发展 行为补偿具体目标是：（1）进一步研究 SMC损伤诱导的非受损运动学习的增强 前肢，包括其对先天前肢偏好和损伤前的依赖性 （2）测试增强学习与以下假设有关： 损伤引起的运动皮层神经可塑性变化，（3）确定 增强的学习和相关的神经可塑性变化对 损伤诱导的去神经支配和损伤诱导的行为变化，（4）确定 是否有一个敏感的损伤后时间窗口，这些影响和（5） 评估其对功能结局的影响。这些研究将使用 灵敏的行为测量结合定量光， 立即早期基因表达变化的电子显微镜测量， 树突状细胞骨架重构和突触连接的变化 运动皮层这些研究的结果预计将是重大的 与康复工作的关系。

DESCRIPTION (provided by investigator): One of the most reliable consequences of survivable brain damage is that animals undergo major behavioral changes as they attempt to compensate for their impairments. Knowing how these behavioral changes interact with injury-induced brain changes may be critical for understanding neural and behavioral adaptation to brain damage. This research will investigate the possibility that the partial denervation that occurs in a connected region after focal cortical injury promotes some types of learning and the neuronal changes underlying this learning. The ability of rats with unilateral damage to the forelimb region of the sensorimotor cortex (SMC) to acquire skilled motor tasks with the non-impaired forelimb has recently been found to be enhanced in comparison to their intact counterparts. It is hypothesized that the enhancement of motor learning results because mild lesion-induced degenerative events facilitate the neuronal changes underlying this learning in the primary motor cortex opposite the lesion. Because these lesions cause the rats to rely on this limb, this provides a unique model system to investigate neural mechanisms underlying the development of behavioral compensation. The specific goals are to: (1) further investigate the SMC lesion-induced enhancement of motor learning with the non-impaired forelimb, including its dependency on innate forelimb preferences and preinjury training, (2) test the hypothesis that the enhanced learning is linked to lesion-induced neuroplastic changes in the motor cortex, (3) determine the dependency of the enhanced learning and associated neuroplastic changes on lesion-induced denervation and lesion-induced behavioral changes, (4) determine whether there is a sensitive post-injury time window for these effects and (5) assess their implications for functional outcome. These studies will use sensitive behavioral measures in combination with quantitative light and electron microscopic measures of changes in immediate early gene expression, dendritic cytoskeletal restructuring and changes in synaptic connections in the motor cortex. The results or these studies are expected to be of major relevance to rehabilitation efforts.