NITRIC OXIDE AND FUNCTIONAL PLASTICITY

一氧化氮与功能性可塑性

• 批准号: 2272779
• 负责人: JOEL H GREENBERG
• 金额: $ 25.67万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-15 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2272779
• 关键词: autoradiography; brain electrical activity; brain injury; brain metabolism; denervation; enzyme inhibitors; glucose metabolism; laboratory rat; membrane potentials; neural information processing; neural plasticity; nitric oxide; nitric oxide synthase; radionuclide double label; sense organs

DESCRIPTION (Investigator's Abstract): One of the long term interests of this laboratory has been the study of the relationship between cerebral blood flow and metabolism. There is evidence in the literature that nitric oxide is involved in both long-term potentiation and long- term depression and may also be involved in learning. These data all suggest a role for nitric oxide in activity dependent plasticity. This project will utilize a well characterized model of functional activation and plasticity to examine the role that nitric oxide plays in cerebral metabolic and flow plasticity and in the relationship between cerebral blood flow and metabolism. The model selected is the precisely organized rat facial vibrissa (whisker)-first somatosensory (S1) cortical "barrel" sensory system. The precise organization of this system, coupled with the fact that the vibrissae are important tactile receptors in the rat's normal behavior, makes this an ideal system to investigate plasticity following either peripheral or central injury. The specific aims of this project are to characterize the degree of functional reorganization of the adult somatosensory cortex following a peripheral lesion, and to determine the role of nitric oxide on this reorganization. Functional reorganization will be assessed with a double-label autoradiographic measurement of local cerebral glucose utilization (using [18F]fluorodeoxyglueose), and local cerebral blood flow (using [14C]iodoantipyrine), as well as with multiple site extracellular recordings of evoked multi-unit spike activity in S1 barrel cortex. Two preparations will be employed to examine plasticity in the somatosensory system. The first employs an unilateral deafferentation-spared vibrissa model in which all vibrissae, except one (#3 of row 6; SC3), are ablated in the adult rat followed two months later by measurements of local cerebral glucose utilization and local cerebral blood flow. In the intervening time, measurements of multi-unit activity will be made in the region of the S1 SC3. In these studies the nitric oxide/arginine system will be manipulated using inhibitors of nitric oxide synthase. This model provides data on the S1 cortical effect of a peripheral lesion. The second preparation employs adult bilateral SC3 deafferentation followed by training or conditioning of one SC3 vibrissa. These latter studies will be undertaken to characterize the metabolic SC3 reorganization of the S1 SC3 representation following unilateral SC3 conditioning, and to determine if changes in the conditioned metabolic representation will be abolished by chronic blockade of nitric oxide synthase. In addition to an examination of functional plasticity, this project will measure changes in the local nitric oxide concentration in the S1 vibrissa barrel bring vibrissa stimulation and will also utilize double label autoradiography to examine the role of nitric oxide in the, flow/metabolism couple. Investigation of the mechanism of functional plasticity, including the role of nitric oxide, provide important information regarding potential recovery of function after peripheral or central injury to the nervous system.

描述(调查者摘要)：长期利益之一 本实验室一直在研究两者之间的关系 脑血流和新陈代谢。文献中有证据表明 一氧化氮参与了长时程增强和长时程增强。 长期抑郁，也可能与学习有关。这些数据都是 提示一氧化氮在活性依赖的可塑性中起作用。这 项目将利用功能激活的特征良好的模型 和可塑性来研究一氧化氮在大脑中所起的作用 代谢与流动可塑性及其在脑组织中的关系 血液流动和新陈代谢。所选模型是经过精确组织的 大鼠面部触觉(胡须)-第一躯体感觉(S1)皮质“桶” 感官系统。这个系统的精确组织，再加上 触须是大鼠大脑中重要的触觉感受器 正常行为，使其成为研究可塑性的理想系统 在周围或中枢性损伤之后。这样做的具体目的是 项目是为了表征功能重组的程度 外周损伤后的成人躯体感觉皮质，以及 确定一氧化氮在这一重组中的作用。功能性 重组将用双标记放射自显影进行评估 局部脑葡萄糖利用的测量(使用 [18F]氟脱氧葡萄糖)和局部脑血流量(使用 [14C]碘安替比林)以及与多个细胞外部位结合 在S1桶皮质诱发的多单位棘波活动的记录。二 准备工作将被用来检测身体感觉的可塑性。 系统。第一种采用单侧去传入--免触觉 除一个(第6行的#3；SC3)外，所有触须都被消融的模型 在两个月后的成年大鼠中，测量局部 脑葡萄糖利用率和局部脑血流量。在 在间隔时间内，多单元活动的测量将在 S1 SC3的区域。在这些研究中，一氧化氮/精氨酸系统 将使用一氧化氮合酶抑制剂进行操作。这 模型提供了外周病变的S1皮质效应的数据。 第二种方法是成人双侧SC3去传入。 然后训练或调节一个SC3触觉。这些是后者 将进行研究以确定新陈代谢SC3的特征 单边SC3之后S1 SC3表示的重组 条件反射，并确定条件化代谢的变化 代表权将因长期阻断一氧化氮而取消 合成酶。除了对功能可塑性的检查外，这一点 该项目将测量当地一氧化氮浓度的变化 S1VERISSA桶带来VERISSA刺激，还将利用 用双标记放射自显影技术检测一氧化氮在 流动/新陈代谢配对。功能障碍发生机制的探讨 可塑性，包括一氧化氮的作用，提供了重要的 有关外周手术后功能可能恢复的信息 或神经系统中枢性损伤。