SLEEP AND SYNAPTIC PLASTICITY

睡眠和突触可塑性

• 批准号: 6042841
• 负责人: JIDONG FANG
• 金额: $ 31.01万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6042841
• 关键词: behavior test; electromyography; genetically modified animals; hippocampus; immunocytochemistry; in situ hybridization; laboratory mouse; learning; neural plasticity; neuroanatomy; neurotrophic factors; nuclear factor kappa beta; sleep; somesthetic sensory cortex; synapses

Several theories concerning sleep function posit that sleep serves to maintain, repair or consolidate synapses. Several lines of evidence support these theories but, to date, there has been no direct test of these hypotheses. An independent large literature relates long-term memory tasks to synaptic plasticity. Further, a few studies have demonstrated a clear influence of sleep on memory consolidation and of learning tasks on sleep. However, there are heretofore, no studies of the influence of sleep on synaptic plasticity despite the theoretical foundation for such studies and the fact that the necessary molecular tools and mouse models are now available. To test the general hypothesis that sleep has a role in synaptic plasticity we will use a non-cognitive stimulus (a unilateral whisker cut) and a cognitive stimulus (a spatial learning test) to induce synaptic plasticity in the somatosensory cotex and the hippocampus respectively. The effects of sleep loss and excess sleep in these experimental paradigms on the magnitude and rates of change of a variety of molecular markers of synaptic plasticity will be determined. The markers to be analyzed represent six classes of molecules necessary for synaptic remodeling; extracellular matrix proteins, cell adhesion molecules, growth factors, neurotransmission related proteins, cytoskeletal and associated proteins and transcription factors. Three strains of mice will be used, AKR/J, acallosal mice and a transgenic strain carrying the lac-Z gene coupled to a promoter dependent upon the presence of nuclear factor Kappa B. In addition to quantifying the changes in the molecular markers of synaptic plasticity in extracts of small areas of the brain, we will also determine the specific location of cell types in which these molecules change in response to sleep manipulation using histochemistry, immunocytochemistry and in situ hybridization histochemistry. Expected results will provide the foundations for the experimental verification of sleep function.

关于睡眠功能的几种理论都认为，睡眠有助于维持、修复或巩固突触。 一些证据支持这些理论，但到目前为止，还没有直接测试这些假设。 一个独立的大型文献将长期记忆任务与突触可塑性联系起来。此外，一些研究已经证明了睡眠对记忆巩固和学习任务对睡眠的明显影响。然而，迄今为止，没有研究睡眠对突触可塑性的影响，尽管这些研究的理论基础和必要的分子工具和小鼠模型现在可用的事实。 为了检验睡眠在突触可塑性中起作用的一般假设，我们将使用非认知刺激（单侧胡须切割）和认知刺激（空间学习测试）分别诱导体感皮质和海马中的突触可塑性。 将确定这些实验范式中睡眠不足和睡眠过多对突触可塑性的各种分子标记物的变化幅度和速率的影响。 待分析的标记物代表突触重塑所需的六类分子：细胞外基质蛋白、细胞粘附分子、生长因子、神经传递相关蛋白、细胞骨架和相关蛋白以及转录因子。 将使用三种小鼠品系，AKR/J、无胼胝体小鼠和携带与依赖于核因子κ B存在的启动子偶联的lac-Z基因的转基因品系。 除了量化大脑小区域提取物中突触可塑性分子标记物的变化外，我们还将使用组织化学、免疫细胞化学和原位杂交确定这些分子响应睡眠操纵而发生变化的细胞类型的具体位置。组织化学。预期结果将为睡眠功能的实验验证提供依据。