NEURAL AND BEHAVIORAL PLASTICITY AFTER BRAIN DAMAGE

我们将继续调查安定和安非他明的破坏性影响 单侧损伤后感觉运动功能恢复的相关药物 到前内侧皮质区域。此外，在此期间进行的实验 目前的资助期导致对小说的额外关注 解剖学事件，似乎在修复过程中起重要作用 功能。这项提案中概述的总体战略是操纵 使用破坏性或促进治疗的恢复过程，以定义 治疗有效的敏感期，以分析 行为的详细信息，并描述 同侧和对侧皮质下和皮质区 半球。我们最近发现，对于受伤的人， 感觉运动皮质厚度的大幅增加仅发生在 对侧半球的同伦面积，然后缩小 厚度增加，但不能完全恢复到基线。的最大增幅 厚度在时间上与过度使用健侧肢体相对应 居家笼式姿势运动行为，尤指具有 负重/转移后果。这增加了一种可能性，即 形态的改变可能与动物采取的行为策略有关 动物用来补偿损伤所致的损伤 对侧前肢。在后续的实验中，我们发现在 厚度增加的区域，随时间的变化显著增长 V层神经元树突，然后部分修剪。修剪可以 表示对恢复更对称的肢体使用的调整，或者可以 与改进的两个前肢的交叉中线协调相对应。我们 计划进一步表征新的两相(生长-修剪)树枝状 序列及其潜在的行为意义，并操纵每个 通过药物和行为干预实现独立阶段，以努力 确定它可能如何参与脑后功能的恢复 损坏。例如，单袖投射或开袖(控制)投射将 用于允许使用同侧、对侧或两个前肢 单侧感觉运动皮质大鼠的笼养行为 损伤或假手术。初步结果表明， 只有在合并脑损伤后，完整的皮质才会出现树枝状结构 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，同时评估时间依赖的影响 药物和行为干预。

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.