Functional Regeneration of Locomotor Command Neurons

运动命令神经元的功能再生

基本信息

批准号：
6920603
负责人：
ANDREW D McCLELLAN
金额：
$ 17.72万
依托单位：
UNIVERSITY OF MISSOURI-COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-09-30 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6920603
关键词：
Agnatha axon chordate locomotion developmental neurobiology motor neurons nervous system regeneration neuroregulation spinal cord injury

项目摘要

In adult "higher" vertebrates, including humans, spinal cord injury can result in permanent behavioral deficits because of very limited axonal regeneration in the CNS and, therefore, this condition remains a serious medical problem. The long-term goals of my research are to understand the cellular and molecular mechanisms that control axonal regeneration of descending brain neurons and recovery of locomotor function after spinal cord injury. The lamprey, a "lower" vertebrate, displays dramatic behavioral recovery after spinal cord transection and has many experimental advantages for examining the mechanisms that control functional axonal regeneration. The present study will investigate five important aspects of axonal regeneration and restoration of locomotor function in spinal cord-transected larval lamprey. (I) (a) Anatomical experiments with lamprey of different ages will test whether some descending brain-spinal cord projections are added during larval life and potentially could contribute to behavioral recovery after spinal cord injury. (b,c) Double labeling will be used to determine if unidentified descending and ascending propriospinal neurons regenerate their axons after spinal cord transection. (II-IV) There are a number of mechanisms that potentially could impact on axonal regeneration and recovery of function, and a better understanding of these mechanisms might lead to methods for enhancing recovery. (II) Intracellular recordings will test whether spinal cord transection results in temporary retraction of synaptic inputs to axotomized descending brain neurons that might compromise sensory-evoked locomotion, particularly at early recovery times. (III) Anatomical experiments will test several mechanisms that might be responsible for different capacities of axonal regeneration of descending brain neurons. (IV) Anatomical and neurophysiological experiments will test the hypothesis that axonal regeneration of descending brain neurons is incomplete because axons grow across a spinal lesion and make synapses, which suppress further regeneration. (V) The hypothesis will be tested that regenerative capacities of axotomized descending brain neurons are not fixed but can be enhanced by a prior "conditioning" spinal cord lesion. Together, these experiments will provide timely and important information that will begin to elucidate the mechanisms that control neural regeneration and behavioral recovery after spinal cord injury in a model vertebrate system.

在包括人类在内的成年“较高”脊椎动物中，脊髓损伤可能导致永久性的行为缺陷，因为中枢神经系统的轴突再生非常有限，因此，这种情况仍然是一个严重的医疗问题。我的研究的长期目标是了解控制脑神经元的轴突再生的细胞和分子机制，以及脊髓损伤后运动功能的恢复。七lamp虫（一种“下”脊椎动物）在脊髓横断后显示出戏剧性的行为恢复，并且在检查控制功能性轴突再生的机制方面具有许多实验优势。本研究将研究轴突再生的五个重要方面和脊髓转移的幼虫七lamp虫中运动功能的恢复。（i）（a）具有不同年龄段的lamp虫的解剖实验将测试是否在幼虫寿命期间添加了一些降低的脑脊髓投影，并且有可能在脊髓损伤后有助于行为恢复。（b，c）双重标记将用于确定脊髓横断后未鉴定的降降和上升的前脊髓神经元是否会再生其轴突。（II-IV）有许多机制可能会影响轴突再生和功能恢复，并且对这些机制的更好理解可能会导致增强恢复的方法。（ii）细胞内记录将测试脊髓横断是否会导致突触输入暂时缩回到轴突降低的脑神经元，这可能会损害感觉引起的诱发的运动，尤其是在早期恢复时间。（iii）解剖实验将测试几种可能导致降低脑神经元轴突再生能力的机制。（iv）解剖学和神经生理实验将检验以下假设：降低脑神经元的轴突再生是不完整的，因为轴突在脊柱病变中生长并产生突触，从而抑制了进一步的再生。（v）将检验该假设，即轴降低脑神经元的再生能力不是固定的，但可以通过先前的“调节”脊髓病变来增强。总之，这些实验将提供及时，重要的信息，这些信息将开始阐明模型脊椎动物系统中脊髓损伤后控制神经再生和行为恢复的机制。