FUNCTIONAL REGENERATION OF LOCOMOTOR COMMAND NEURONS

运动命令神经元的功能再生

• 批准号: 2267356
• 负责人: ANDREW D McCLELLAN
• 金额: $ 13.83万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2267356
• 关键词: Agnatha; brain stem; cell biology; chordate locomotion; denervation; molecular biology; morphology; nervous system regeneration; neural information processing; neural plasticity; neuroanatomy; neurons; neurophysiology; neuropsychology; reticulospinal tract; spinal cord injury; synaptogenesis

The long-term goals of my research are to understand the cellular and molecular mechanisms that control regeneration of descending axons from brain neurons and recovery of locomotor function following spinal cord injury. The lamprey, a "lower" vertebrate, has many experimental advantages for examining the factors that control functional regeneration. Between 2-8 weeks following transection of the rostral spinal cord in larval lamprey, locomotor movements gradually return to normal, and muscle activity can be recorded at progressively greater distances below the lesion. With increasing recovery times, descending axons from brainstem neurons, including reticulospinal (RS) neurons that are thought to initiate locomotor activity, regenerate to progressively more caudal levels of the spinal cord, However, complete restoration of descending projections is not required for recovery of function. Substantial recovery of locomotor function can occur at a particular level of the body below a spinal cord lesion when the descending projections to the corresponding level of the spinal cord are reduced or absent. These results suggest that in higher vertebrates, recovery of locomotor function might occur without substantial regeneration, provided that additional compensatory mechanisms are available. The present study will use neurophysiological, behavioral, and anatomical techniques to examine four aspects of functional regeneration and restoration of locomotor initiation in spinal cord-transected lamprey. (I) The biophysical and morphological properties of axotomized descending brain neurons, particularly RS neurons, will be examine& to determine if the time course of changes in these properties is related to regeneration of descending brainstem projections, synaptic reconnection, and behavioral recovery. (II) Paired intracellular recordings will be made between regenerated RS neurons and neurons in spinal locomotor networks to determine if synaptic specificity is necessary for behavioral recovery. (III) Synaptic inputs and activity patterns in RS neurons will be determined before, during, and after behavioral recovery to investigate plasticity in these neurons relative to the time course of regeneration and synaptic reconnection with spinal targets. (IV) At short recovery times, descending axons from brainstem command neurons have regenerated for short distances below the lesion, and descending propriospinal neurons appear to relay descending drive to locomotor networks in the more caudal areas of the spinal cord. Physiological and anatomical experiments will be used to examine these important descending propriospinal neurons. Together, these experiments will provide critical information that will elucidate the mechanisms controlling spinal cord regeneration and behavioral recovery following spinal injury.

我研究的长期目标是了解细胞和 控制轴突再生的分子机制 脊髓后的脑神经元和运动功能的恢复 受伤。七lamp虫是“下部”脊椎动物，有许多实验性 检查控制功能的因素的优势 再生。延伸后2-8周之间 幼虫七lamp虫的脊髓，运动运动逐渐返回 正常和肌肉活动可以逐渐记录 病变以下的距离。随着恢复时间的增加，下降 来自脑干神经元的轴突，包括网状（RS）神经元 被认为启动运动活动，再生至逐渐 然而，脊髓的更多尾部水平，完全恢复 恢复功能并不需要下降预测。 可以在特定的 下降时的身体水平 降低脊髓相应水平的预测或 缺席的。这些结果表明，在较高的脊椎动物中，恢复 运动功能可能不会在没有实质性再生的情况下发生 可以使用其他补偿机制。 本研究将使用神经生理学，行为和解剖学 研究功能再生的四个方面和 恢复脊髓转换七lamp虫中的运动启动。 （i）轴降降的生物物理和形态学特性 脑神经元，尤其是RS神经元，将检查并确定是否是否 这些属性变化的时间过程与再生有关 脑干的降临，突触重新连接和 行为恢复。 （ii）将进行配对的细胞内记录 在脊柱运动网络中再生的RS神经元和神经元之间 确定行为是否需要突触特异性 恢复。 （iii）RS神经元中的突触输入和活动模式将 在行为恢复之前，之中和之后确定 研究这些神经元相对于时间过程的可塑性 与脊柱靶标的再生和突触重新连接。 （iv）简而言 恢复时间，脑干命令神经元的降轴突有 在病变以下的短距离内再生，并下降 周期性神经元似乎将降落驱动器转向运动 脊髓更尾端的网络。生理和 解剖实验将用于检查这些重要的下降 周期性神经元。这些实验将共同提供关键 将阐明控制脊髓的机制的信息 脊柱损伤后的再生和行为恢复。