PHYSIOLOGICAL CORRELATES OF NEURAL PLASTICITY

这项研究的长期目标是确定 功能恢复和改变的基础机制 在成年哺乳动物中枢神经部分去神经后， 神经系统 该项目以前的工作导致了新的 假设来解释短期和长期的生理 脊髓背角细胞的变化 中断下行通路。 拟议将 对外周刺激（“脊髓刺激”）的反应性立即下降 休克”）是由于失去下行抑制作用， 介导传入神经突触前抑制的中间神经元 活动 据推测， 对外围设备输入的响应能力， 自发活动恢复到正常水平是由于 去神经超敏反应。 建议的实验是 旨在测试这些假设和替代方案，更多 传统的假设认为脊髓休克是由于 与急性损伤本身有关， 对周围刺激的反应是由于释放 下行抑制 为了测试脊髓休克是否是由于损伤本身，申请人 计划测量背角细胞对周围神经的反应性， 刺激后急性背外侧索病变和比较 这与DLF急性阻断下的反应性有关， 利多卡因微量注射 为了测试背角细胞是否 在紧张性下行突触后抑制下，细胞内 方法将被用来测量他们的膜电位之前， 和利多卡因阻断DLF后。 要测试主 传入纤维处于紧张性突触前抑制，背根 初级传入神经的电位和微刺激阈值 在利多卡因阻滞之前和之后测量末端。 去神经超敏反应的发展。 的 微量注射5-羟色胺和肽类神经递质 对背角神经元的反应特性进行评估 在正常和DLF损伤动物中，存活时间为< 1至60 天 这些研究有助于我们理解 中枢神经系统损伤的生理后果，以及 神经系统适应这种损伤的能力。

The long-term objective of this research is to determine the mechanisms that underlie recovery and alteration of function following partial denervation of the adult mammalian central nervous system. Previous work on this project has led to new hypotheses to explain the immediate and long term physiological changes observed in spinal cord dorsal horn cells following interruption of descending pathways. It is proposed that the immediate decline in responsiveness to peripheral stimuli ("spinal shock") is due to a loss of descending inhibition acting on interneurons that mediate presynaptic inhibition of afferent activity. It is postulated that the long term recovery of responsiveness to peripheral inputs and eventual return of spontaneous activity to normal levels are due to the development of denervation supersensitivity. The proposed experiments are designed to test these hypotheses and the alternative, more conventional hypotheses that spinal shock is due to mechanisms related to acute injury per se, and that long-term increases in responsiveness to peripheral stimuli are due to release of descending inhibition. To test whether spinal shock is due to injury per se, the applicant plans to measure dorsal horn cell responsiveness to peripheral stimuli following acute dorsolateral funiculus lesions and compare this with responsiveness under acute blockade of the DLF by lidocaine microinjection. To test whether dorsal horn cells are under tonic descending postsynaptic inhibition, intracellular methods will be used to measure their membrane potentials before and after lidocaine blockade of the DLF. To test whether primary afferent fibers are under tonic presynaptic inhibition, dorsal root potentials and microstimulation thresholds of primary afferent terminals will be measured before and after lidocaine blockade. To test for the development of denervation supersensitivity. The effects of microinjecting serotonin and peptide neurotransmitters on the response properties of dorsal horn neurons will be evaluated in normal and DLF lesion animals at survival times from < 1 to 60 days. These studies are relevant to our understanding of the physiological consequences of central nervous system injury, and of the ability of the nervous system to adapt to such injury.