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：
2267355
负责人：
ANDREW D McCLELLAN
金额：
$ 9.44万
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 1995-03-31
项目状态：
已结题

项目摘要

In normal lampreys some of the brainstem command neurons which initiate locomotion are reticulospinal (RS) neurons in the medial and posterior rhombencephalic reticular nuclei (MRRN and PRRN) that have descending axons in the latcral spinal tracts (64,65). These particular RS neurons are different than the large, identifiable Muller cells, which have their axons in the medial spinal tracts and do not contribute significantly to the initiation of locomotion. Following a complete spinal transection, larval lamprey recover locomotor function within 3-6 wks., and part of this recovery process is due to functional regeneration of descending axons arising from brainstem command neurons that have grown across the transection site and can activate the spinal locomotor networks below the lesion (61,63). In the present study the extent, time course, and specificity of this regeneration will be examined. Many of the experiments will use an in vitro brain/spinal cord preparation, in which the extracellular environment can be manipulated and intracellular recordings arc easily performed. The goals of the project are to examine four aspects of regeneration of R neurons that initiate locomotion in spinal-transected lamprey. (1) At least some of the growth of descending axons following a spinal transection is due to true neural regeneration of pre-existing R neurons. Cell markers, double labeling, and bromodeoxyuridine incorporation will be used to determine if development of new R neurons is also partly involved. (II) The extent of regeneration of descending R axons will be examined with both neurophysiological and anatomical methods. (III) In normal animals, R command neurons have axons in the lateral spinal tracts, and some of these axons only project to the rostral spinal cord while others project to more caudal regions. Physiological and anatomical methods will be used to determine if regenerating descending axons retain a certain degree of specificity and regrow in the same spinal tracts and to the same levels of the spinal cord as in normal animals. (IV) The biophysical properties and morphologies of R neurons will be compared in control animals (66) and animals that are recovering or have recovered from spinal transections. In addition, paired intracellular recordings will bc made from regenerated R neurons and spinal neurons to determine if normal connections have been restored. Together, these experiments will provide new information that will help us understand spinal cord regeneration and behavioral recovery following spinal injury. In the future, manipulations, such as spinal cord rotations and translocations, will be made to determine some of the intrinsic and extrinsic factors that affect the extent and specificity of regeneration.

在普通的lampreys中，一些脑干命令神经元启动运动是内侧和后部的网状神经元（RS）神经元轴突降轴突的老虎脑网核（MRRN和PRRN）在上线脊柱中（64,65）。这些特殊的RS神经元是与具有轴突的大型，可识别的穆勒细胞不同在内侧脊柱中，没有显着贡献运动的启动。完整的脊柱横向后，幼虫七lamp虫恢复3-6周内的运动功能，其中一部分恢复过程是由于降轴突的功能再生由脑干命令神经元引起的横切部位，可以激活下方的脊柱运动网络病变（61,63）。在本研究中，时间课程和将检查这种再生的特异性。许多实验将使用体外大脑/脊髓制剂，其中可以操纵细胞外环境和细胞内记录弧很容易执行。该项目的目标是检查R的再生四个方面在脊柱转移的七lamp虫中引发运动的神经元。（1）至少脊柱横断后降轴突的某些生长是由于现有的R神经元的真正神经再生。细胞标记，双重标记和溴脱氧尿苷掺入将用于确定新R神经元的发展是否也部分涉及。（ii）两者都将检查下降r轴突再生的程度神经生理和解剖学方法。（iii）在普通动物中，r 命令神经元在脊柱外侧有轴突，其中一些仅轴突向脊髓伸出，而其他则投影到更多尾区。生理和解剖方法将用于确定再生是否保留一定程度的在相同的脊柱和相同水平的特异性和再生脊髓和普通动物一样。（iv）生物物理特性和对照动物（66）和正在恢复或从脊柱过渡中恢复的动物。在此外，配对的细胞内记录将由再生R制成的BC 神经元和脊髓神经元以确定正常连接是否已恢复。这些实验将共同提供新信息将帮助我们了解脊髓再生和行为恢复脊柱损伤后。将来，操作，例如脊髓旋转和易位将进行确定的一些影响的固有和外在因素会影响再生。