Regulation Of Neuronal Gene Expression By Action Potenti

通过动作电位调节神经元基因表达

• 批准号: 6534885
• 负责人: RICHARD DOUGLAS FIELDS
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6534885
• 关键词: Schwann cells; action potentials; biological signal transduction; cadherins; cell adhesion; cell adhesion molecules; developmental genetics; developmental neurobiology; gene induction /repression; genetic transcription; myelin; neural conduction; neural transmission; neurogenesis; neurons; neurophysiology; neurotrophic factors; regulatory gene; spinal ganglion; tissue /cell culture; vertebrate embryology

Research in the Unit on Neurocytology and Physiology, is concerned with understanding how the brain develops and modifies its structure and function through experience. Functional activity in the brain during late stages of fetal development and in early postnatal life is essential for normal development of the nervous system of higher vertebrates. Our research is investigating the molecular mechanisms that enable neural impulse activity to regulate major developmental processes of both neurons and glia. This main objectives of this research program are: (1) to understand how the expression of genes controlling the developing structure and function of the nervous system are regulated by patterned neural impulse activity; (2) to determine the functional consequences of neural impulse activity on major developmental processes, including: cell proliferation, survival, differentiation, growth cone motility, axon bundling (fasciculation), neurite outgrowth, synaptogenesis and synapse remodeling, myelination, interactions with glia, and the mechanisms of learning and memory in postnatal animals; (3) to understand how information contained in the temporal pattern of neural impulse activity is transduced and integrated within the intracellular signaling networks of neurons to activate specific genes and control appropriate adaptive responses. Major achievements of research in the last year include: (1) the discovery that development of glia of the peripheral and central nervous system (Schwann cells and oligodendrocytes) is regulated by neural impulse activity in premyelinated neurons, and determined that extracellular ATP and related molecules communicate neural impulse activity in neurons to glia; (2) tested the hypothesis that a key signaling protein activated by neural impulse activity and involved in LTP, calcium-calmodulin dependent protein kinase II (CaM KII) can decode different frequencies of action potentials by autophosphorylation at Thr-286; (3) determined that different calcium-dependent signaling pathways are activated in CA1 neurons by different stimulus patterns to phosphorylate the signaling molecule MAPK in association with long-term potentiation (LTP) in the hippocampus; used DNA microarrays to study gene expression profiles in neurons in response to specific patterns of neural impulses.

神经细胞学和生理学单元的研究涉及了解大脑如何通过经验发育和改变其结构和功能。胎儿发育后期和出生后早期的大脑功能活动对于高等脊椎动物神经系统的正常发育至关重要。我们的研究正在研究使神经冲动活动能够调节神经元和神经胶质细胞主要发育过程的分子机制。该研究计划的主要目标是：（1）了解控制神经系统发育结构和功能的基因表达如何受到模式化神经冲动活动的调节； (2) 确定神经冲动活动对主要发育过程的功能影响，包括：细胞增殖、存活、分化、生长锥运动、轴突成束（束颤）、神经突生长、突触发生和突触重塑、髓鞘形成、与神经胶质细胞的相互作用，以及产后动物的学习和记忆机制； （3）了解神经冲动活动的时间模式中包含的信息如何在神经元的细胞内信号网络中转导和整合，以激活特定基因并控制适当的适应性反应。去年的主要研究成果包括：（1）发现周围和中枢神经系统（雪旺细胞和少突胶质细胞）胶质细胞的发育受髓鞘前神经元神经冲动活动的调节，并确定细胞外ATP及相关分子将神经元中的神经冲动活动传达给神经胶质细胞； (2) 验证了神经冲动激活并参与LTP的关键信号蛋白钙钙调蛋白依赖性蛋白激酶II (CaM KII)可以通过Thr-286处的自磷酸化解码不同频率的动作电位的假设； (3)确定不同的刺激模式在CA1神经元中激活不同的钙依赖性信号通路，从而磷酸化与海马长时程增强(LTP)相关的信号分子MAPK；使用 DNA 微阵列来研究神经元中响应特定神经脉冲模式的基因表达谱。