NITRIC OXIDE AND FUNCTIONAL PLASTICITY

描述（研究者摘要）：长期利益之一 这个实验室的一项研究就是 脑血流量和代谢。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， 长期抑郁症，也可能涉及学习。这些数据都 提示一氧化氮在活动依赖性可塑性中作用。这 项目将利用功能激活的良好表征模型 和可塑性来研究一氧化氮在脑内 代谢和流动可塑性以及大脑 血液流动和新陈代谢。选择的模型是精确组织的 大鼠面部触须（须）-第一体感（S1）皮质“桶” 感觉系统这个系统的精确组织， 事实上，触须是老鼠的重要触觉感受器， 正常行为，使其成为研究可塑性的理想系统 无论是外周还是中枢损伤。具体目标是 项目的特点是功能重组的程度， 周围损伤后的成人躯体感觉皮层，以及 确定一氧化氮在这种重组中的作用。功能 将使用双标记放射自显影评估重组 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 [14 C]碘安替比林），以及与细胞外多位点 记录S1桶皮质中诱发的多单位锋电位活动。两 准备将被用来检查可塑性的躯体感觉 系统第一种采用单侧传入神经切断--保留触须 除一根（第6行第3根; SC 3）外，所有触须均被消融的模型 在成年大鼠中，两个月后通过测量局部 脑葡萄糖利用和局部脑血流量。在 干预时间，多单位活动的测量将在 在S1 SC 3区。 在这些研究中， 会被一氧化氮合酶抑制剂控制 这 模型提供了关于外周病变的S1皮质效应的数据。 第二种制备方法采用成人双侧SC 3传入神经阻滞 随后训练或调节一根SC 3触须。这些后者 将进行研究以表征代谢SC 3 单侧SC 3后S1 SC 3代表的重组 条件反射，并确定条件反射代谢的变化 代表性将被慢性阻断一氧化氮 合成酶 除了检查功能可塑性， 该项目将测量当地一氧化氮浓度的变化， S1鼻毛桶带来鼻毛刺激，也将利用 双标记放射自显影以检查一氧化氮在， 血流/代谢偶联。 功能性的作用机理探讨 可塑性，包括一氧化氮的作用，提供重要的 关于外围设备术后功能恢复的潜在信息 或中枢神经系统损伤。

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.