Learning Within the Spinal Cord: Clinical Implications

脊髓内的学习：临床意义

• 批准号: 6621602
• 负责人: James William Grau
• 金额: $ 38.19万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6621602
• 关键词: behavior test; behavioral /social science research tag; conditioning; fos protein; functional ability; immunocytochemistry; laboratory rat; learning; neural plasticity; neurochemistry; spinal cord; spinal cord injury

DESCRIPTION (provided by applicant): Traditionally, the spinal cord has been viewed as a conduit between the brain and the periphery, organizing some simple reflexes but otherwise contributing little to learning and behavior. However, recent studies suggest that a great deal of information processing occurs within the spinal cord, and that this system not only tunes the afferent and efferent input/output at the brain's bidding but also adapts on its own to new environmental relations. Learning within the spinai cord can be studied using rats that have had the spinal cord cut at the second thoracic vertebra. A response-outcome contingency is established by applying shock to one hindleg whenever the leg falls below a preset criterion. Spinal neurons appear sensitive to this instrumental contingency, for subjects quickly learn to maintain their leg in a flexed position, effectively minimizing exposure to shock. This instrumental learning is facilitated by prior exposure to contingent shock and disrupted by noncontingent shock. It appears contingent training enables behavioral potential while noxious noncontingent stimuli undermine behavioral potential. The proposed experiments focus on the mechanisms that foster and preserve behavioral plasticity within the spinal cord and the implications of this work for the recovery of function after spinal cord injury. Studies proposed will examine the retention of the facilitory effect, the impact of Pavlovian contingencies, and whether clinically relevant stimuli (nerve injury, inflammation) affect behavioral potential. It is suggested that some neurochemical systems (noradrenergic, and/or serotonergic) may help preserve behavioral potential. Experiments will examine whether engaging these systems protects the spinal cord from the deleterious effects of noncontingent noxious stimuli. Finally, studies will explore the underlying mechanisms using immunocytochemical techniques (c-fos) and whether the experimental manipulations affect the recovery of locomotor behavior after a contusion injury. It is hoped that discovering the mechanisms that promote and protect behavioral plasticity within the spinal cord will lead to new behavioral and pharmacological treatments that foster recovery of function after spinal cord injury.

描述（由申请人提供）：传统上，脊髓 被视为大脑和外围设备之间的管道，组织一些简单的 反应，但在其他方面对学习和行为贡献不大。然而， 最近的研究表明，大量的信息处理发生 在脊髓内，这个系统不仅调节传入和 传出输入/输出听从大脑的指挥，但也会自行适应新的 环境关系。 可以使用已经经历过脊髓损伤的老鼠来研究脊髓内的学习能力 在第二胸椎处切断脊髓。响应结果偶然事件 每当一条后腿跌落到低于 预设标准。脊髓神经元似乎对这种乐器敏感 应急措施，让受试者快速学会保持腿部弯曲 位置，有效地最大限度地减少冲击。这种器乐学习 先前暴露于偶然的冲击会促进并受到干扰 非偶然的冲击。看来应急训练可以使行为 潜力，而有害的非偶然刺激会破坏行为潜力。 拟议的实验重点关注促进和保护的机制 脊髓内的行为可塑性以及这项工作的意义 用于脊髓损伤后功能的恢复。拟议的研究将 检查促进效应的保留、巴甫洛夫的影响 意外事件，以及是否有临床相关的刺激（神经损伤、 炎症）影响行为潜力。建议一些 神经化学系统（去甲肾上腺素能和/或血清素能）可能有助于保存 行为潜力。实验将检验这些系统是否参与 保护脊髓免受非偶然有害物质的有害影响 刺激。最后，研究将探索使用的潜在机制 免疫细胞化学技术（c-fos）以及实验是否 操作影响挫伤后运动行为的恢复 受伤。 希望发现促进和保护行为的机制 脊髓内的可塑性将导致新的行为和 促进脊髓损伤后功能恢复的药物治疗 受伤。