Corticospinal development after cortical inactivation

描述(申请人提供)：拟议实验的目标是了解皮质活动在猫皮质脊髓系统发育中的作用。猫的CS系统在出生时是不成熟的，并在出生后早期继续发育。发育过程中的神经活动似乎在决定CS系统的局部组织和在CS轴突与其在脊髓中的神经元靶点之间建立特定的、功能上的连接方面起着至关重要的作用。拟议的实验将确定神经营养因子BDNF和NT-3在发育过程中相对于CS发育的关键期的地形分布。在第二系列实验中，感觉-运动皮质将在发育早期沉默。然后，强制诱导运动疗法或锥体束刺激将实施四周。这一目标将决定康复方案在引导CS向更正常的模式发展方面的效果。由于人类CS发育异常往往导致永久性残疾，了解导致CS发育异常的因素，以及行为干预在引导CS系统走向更正常发育方面的有效性，具有非常重要的临床意义。

DESCRIPTION (provided by applicant): The goal of the proposed experiments is to understand the role of cortical activity in the development of the corticospinal (CS) system in the cat. The cat CS system is immature at birth and continues to develop during early postnatal life. Neural activity during development appears to play a vital role in determining the topographic organization of the CS system and in establishing specific, functional connections between CS axons and their neuronal targets in the spinal cord. The proposed experiments will determine the topographic distribution of the neurotrophins BDNF and NT-3 during development, with respect to the critical period for CS development. In a second series of experiments, sensory-motor cortex will be silenced early in development. Then, either constraint-induced movement therapy or pyramidal tract stimulation will be implemented for four weeks. This aim will determine the efficacy of the rehabilitation regimens in guiding CS development toward a more normal pattern. Since abnormal CS development in humans often results in permanent disabilities, understanding the factors that cause abnormal CS development, and the efficacy of behavioral interventions in guiding the CS system toward a more normal development, is highly clinically significant.