Functional Organization of the Somatosensory System

描述（由申请人提供）：手部传入神经在脊髓背柱传递过程中受到损伤后，脑干突起核、体感丘脑和体感皮层的缺失部分对触觉刺激失去反应，手部使用受损。然而，在1 - 2个月内，皮层可以被一些幸存的背柱传入事件重新激活，手的使用也会改善。我们将评估(1)手部使用的恢复，(2)皮层再激活的时间过程，(3)皮层神经元响应特性的恢复，(4)下脑干楔形核中存活的背柱传入事件的发芽和生长，以接触更多的神经元，以及(5)部分传入神经缺失在楔形核中的细胞和组织化学后果。此外，我们将评估(6)软骨素酶ABC和(7)抗nogo - a两种治疗方法对楔形核中存活的背柱传入神经的新生长的有效性。本研究旨在了解人类感觉丧失后体感觉系统功能恢复的主要机制，并帮助开发对脊髓损伤后感觉丧失的人类有利的治疗方法。公共卫生相关性：提出的研究旨在评估这样一种假设，即脊髓损伤背柱中保存的一些感觉传入神经可以通过萌芽激活脑干和皮层中的大量神经元来介导手部使用的恢复。拟议的研究还将评估两种可能促进保存的感觉传入神经生长的治疗方法。

Description (provided by applicant): After damage to afferents from the hand as they course in the dorsal columns of the spinal cord, deprived portions of the brainstem cuneate nucleus, somatosensory thalamus, and somatosensory cortex become unresponsive to tactile stimuli and hand use is impaired. However, within 1 - 2 months, cortex can be reactivated by a few surviving dorsal column afferents, and hand use improves. We will evaluate the relationships between (1) the recovery of hand use, (2) the time course of the reactivation of cortex, (3) the recovery of response properties of cortical neurons, (4) the sprouting and growth of surviving dorsal column afferents in the cuneate nucleus of the lower brainstem to contact more neurons, and (5) the cellular and histochemical consequences in the cuneate nucleus of partial deafferentation. In addition, we will evaluate the effectiveness of two treatments, (6) chondroitinase ABC and (7) anti-Nogo-A, on sprouting new growth of surviving dorsal column afferents in the cuneate nucleus. The research is designed to provide an understanding of the major mechanisms of recovery of somatosensory system function after a sensory loss in humans, and to help develop favorable therapeutic approaches for humans with sensory loss after spinal cord injury. PUBLIC HEALTH RELEVANCE: The proposed research seeks to evaluate the hypothesis that a few preserved sensory afferents in the dorsal columns of the spinal cord injury can mediate the recovery of hand use by sprouting to activate a large population of neurons in the brainstem and thereby, the cortex. The proposed research will also evaluate two treatments that are likely to promote the growth of the preserved sensory afferents.