Nervous System Development and Plasticity

神经系统发育和可塑性

• 批准号: 7333914
• 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/7333914
• 关键词: Nervous; System; Development; Plasticity

Research in the Section on Nervous System Development and Plasticity, 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 life. The two 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 the last year include showing that myelination is regulated by electrical activity, and that the mechanism involves astrocytes releasing LIF in response to ATP liberated by axons firing action potentials. LIF stimulates myelination by mature oligodendrocytes. Other achievements include identifying changes in gene expression associated with conversion of e-LTP to l-LTP, a cellular model for conversion of short-term to long term memory; identifying activity-dependent interactions between neurons and glia, including how myelination in the PNS and CNS is regulated by axonal firing; detecting an adenosine receptor in Schwann cells (A2a receptor) that is important in regulating Schwann cell development according to action potential firing; identifying intracellular calcium signaling networks regulating gene expression and synaptic plasticity; and identifying genes that are abnormally expressed in a peripheral nerve sheath tumor.

神经系统发育和可塑性部分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。该研究计划的两个主要目标是：（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。 去年的主要成就包括表明髓鞘形成受电活动调节，其机制涉及星形胶质细胞响应轴突激发动作电位释放的 ATP 释放 LIF。 LIF 刺激成熟少突胶质细胞的髓鞘形成。其他成就包括识别与 e-LTP 向 l-LTP 转化相关的基因表达变化，这是一种将短期记忆转化为长期记忆的细胞模型；识别神经元和神经胶质细胞之间的活动依赖性相互作用，包括三七总神经系统和中枢神经系统的髓鞘形成如何受到轴突放电的调节；检测雪旺细胞中的腺苷受体（A2a 受体），该受体对于根据动作电位放电调节雪旺细胞发育非常重要；识别调节基因表达和突触可塑性的细胞内钙信号网络；并鉴定在周围神经鞘瘤中异常表达的基因。