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: 6690429
• 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/6690429
• 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 the molecular mechanisms by which functional activity in the brain regulates development of the nervous system during late stages of fetal development and early postnatal live. The 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. 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 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 how gene expression is activated to convert a model of short-term memory into long-term memory (e-LTP to l-LTP)), and used DNA microarrays to obtain gene expression profiles in neurons in response to specific patterns of neural impulses.

神经细胞学和生理学部门的研究涉及了解大脑功能活动在胎儿发育后期和产后早期调节神经系统发育的分子机制。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。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) 确定基因表达如何被激活以将短期记忆模型转化为长期记忆（e-LTP 到 l-LTP）），并使用 DNA 微阵列获得神经元中响应特定模式的基因表达谱的神经冲动。