NEURAL AND BEHAVIORAL PLASTICITY AFTER BRAIN DAMAGE

我们将继续调查安定的破坏性影响， 相关药物对单侧损伤后感觉运动功能恢复的影响 前内侧皮质区 此外，实验期间， 目前供资期间， 解剖学事件，似乎有一个重要的作用，在恢复 功能 该提案中概述的总体策略是操纵 使用破坏性或促进性治疗的恢复过程，以确定 敏感期，在此期间，治疗是有效的，以分析 行为，并描述相关的结构变化， 同侧和对侧的皮质下和皮质区域 半球 我们最近发现，在应对损伤的 感觉运动皮层厚度的大幅增加仅发生在 对侧大脑半球的同伦区域，然后减少 但没有完全恢复到基线。 最大增加额 厚度与过度使用未受损肢体的时间相对应， 家居笼姿势运动行为，尤其是运动 负重/移位的后果。 这就提出了一种可能性， 形态变化可能与采取的行为策略有关， 动物，以弥补病变引起的损伤， 对侧前肢 在后续实验中，我们发现， 在厚度增加的区域， 第V层神经元树突，随后进行部分修剪。 修剪可 代表对恢复更对称的肢体使用的调整，或者可以 对应于改善的两个前肢的跨中线协调。 我们 计划进一步表征新的双相（生长修剪）树突状细胞 序列及其潜在的行为意义，并操纵每一个 通过药物和行为干预， 确定它如何参与脑损伤后的功能恢复 损害 例如，一个套筒铸件或开放式套筒（对照）铸件将 用于允许使用同侧、对侧或双侧前肢 单侧感觉运动皮层大鼠的笼内行为 损伤或假手术。 初步结果表明， 完整皮层的树枝状化仅发生在脑损伤后， 有肢体使用经验 长期目标是更好地理解 脑损伤后的可塑性，同时评估 药理学和行为干预。

We will continue to investigate the disruptive effects of diazepam and related drugs on recovery of sensorimotor function after unilateral damage to anteromedial cortical regions. Moreover, experiments carried out during the current funding period have led to an additional focus on novel anatomical events that appear to have an important role in restoration of function. The general strategy outlined in this proposal is to manipulate the recovery process using disruptive or facilitating treatments, to define sensitive periods during which the treatments are effective, to analyze behavior in detail, and to describe relevant structural changes in subcortical and cortical regions of the ipsilateral and contralateral hemisphere. We very recently found that in response to injury of the sensorimotor cortex a large increase in thickness occurred exclusively in the homotopic area of the contralateral hemisphere, followed by a reduction in thickness but not a complete return to baseline. Maximum increases in thickness corresponded in time with excessive use of the unimpaired limb in home-cage postural-motor behavior, especially movements having weight-bearing/shifting consequences. This raises the possibility that the morphological changes may be related to behavioral strategies adopted by the animals to compensate for lesion-induced impairments in the contralateral forelimb. In a followup experiment, we found that in the region of increased thickness there was a time-dependent dramatic growth of layer V neuronal dendrites, followed by partial pruning. Pruning may represent an adjustment to the recovery of more symmetrical limb use or may correspond to improved cross-midline coordination of both forelimbs. We plan to characterize further the novel biphasic (growth-pruning) dendritic sequence and its potential behavioral significance, and to manipulate each phase independently by drug and behavioral interventions in an effort to establish how it might be involved in restoration of function after brain damage. For example, one sleeve casts or open-sleeve (control) casts will be used to permit use of the ipsilateral, contralateral, or both forelimbs during home-cage behaviors in rats with unilateral sensorimotor cortex lesions or sham operations. Preliminary results suggest that the dramatic arborization in the intact cortex occurs only after brain injury combined with limb use experience. The long-term goal is to better understand plasticity after brain damage while assessing time-dependent influences of pharmacological and behavioral interventions.