SPINAL CORD PLASTICITY: BEHAVIORAL AND NEURAL MECHANISMS

传统上，脊髓被认为是大脑和周围神经之间的管道，组织一些简单的反射，但对学习和行为几乎没有贡献。 然而，最近的研究表明，大量的信息处理发生在脊髓内，并且该系统不仅根据大脑的命令调整传入和传出输入/输出，而且还自行适应新的环境关系。脊髓内的学习可以使用在第二胸椎（T2）处经历脊髓横断的大鼠来研究。 当一条腿的福尔斯低于预设标准时，通过对该腿施加电击来建立反应-结果应急。 脊髓神经元似乎对这种工具性的偶然性很敏感，因为受试者很快就学会了保持腿部弯曲的姿势，有效地减少了电击的暴露。 破坏反应-结果关系会消除这种学习。 NMDA拮抗剂APV也是如此。 经历了相同数量的电击的大鼠不依赖于腿的位置（非偶然的），无法学习。此外，先前暴露于非偶发性休克破坏学习和/或表现时，偶发性休克是适用于对侧腿，行为缺陷，持续至少24小时。我们提出的实验研究脊髓内工具性学习的机制及其与其他行为现象的关系。 我们建议改进用于研究工具性学习的方法。 然后，我们将探讨学习的局限性，以及工具性偶然性是否会影响中枢敏感化的诱导。其他实验将进一步详细说明非偶发性休克后观察到的行为缺陷的性质，脊髓上系统是否可以抑制其诱导，缺陷持续多长时间，是否可以预防或逆转，以及阿片肽的作用。我们的研究涉及广泛的主题，从学习和记忆的神经生物学到伤害性可塑性和疼痛。 除了这些一般性的问题，脊髓可塑性的理解，它的局限性，它是如何被破坏，以及它如何可以恢复，可能被证明是必不可少的脊髓损伤后的功能恢复。

Traditionally, the spinal cord was 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 spinal cord can be studied using rats that have undergone a spinal transection at the second thoracic vertebra (T2). 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. Disrupting the response-outcome relation eliminates this learning. So too does the NMDA antagonist APV. Rats that have experienced the same amount of shock independent of leg position (noncontingent) fail to learn. Moreover, prior exposure to noncontingent shock undermines learning and/or performance when contingent shock is applied to the contralateral leg, a behavioral deficit that lasts at least 24 hrs. The experiments we propose examine the mechanisms that underlie instrumental learning within the spinal cord and its relation to other behavioral phenomenon. We propose to refine the methodology used to study instrumental learning. We will then explore the limits of learning, and whether the instrumental contingency affects the induction of central sensitization. Other experiments will further detail the nature of the behavioral deficit observed after noncontingent shock, whether supraspinal systems can inhibit its induction, how long the deficit lasts, whether it can be prevented or reversed, and the role of opioid peptides. Our studies speak to a broad range of topics, from the neurobiology of learning and memory to nociceptive plasticity and pain. Beyond these general concerns, an understanding of spinal cord plasticity, its limitations, how it is disrupted, and how it can be restored, may prove essential to the recovery of function after spinal cord injury.