ROLE OF EXCITATORY AMINO ACIDS IN CORTEX DEVELOPMENT

兴奋性氨基酸在皮质发育中的作用

• 批准号: 3478217
• 负责人: Mary E Blue
• 金额: $ 9.43万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3478217
• 关键词: NMDA receptors; autoradiography; brain mapping; cerebral cortex; denervation; developmental neurobiology; excitatory aminoacid; histochemistry /cytochemistry; immunocytochemistry; laboratory rat; learning; memory; neural plasticity; neurotoxins; phencyclidine; receptor binding; receptor expression; receptor sensitivity; serotonin

The long term objective of this research is to understand the role that excitatory amino acid transmitters (EAAs) play in cortical morphogenesis and plasticity. The receptors that mediate the actions of EAAs are present in the developing brain and have been shown to play a role in models of learning and memory and in developmental plasticity. The proposed experiments will examine the role of EAA receptors in the normal development of rodent barrel field cortex and their role in the structural reassignment of cortex which occurs after neonatal peripheral deafferentation. The specific aims are 1) to characterize the ontogeny of EAA receptors in the whisker (peripheral input) to barrel (cortex) pathway, 2) to determine whether changes in EAAs caused by neonatal administration of EAA receptor antagonists will alter barrel formation, 3) to determine whether neonatal administration of the serotonergic neurotoxin, PCA, delays the development of EAA receptor expression in the whisker to barrel pathway, 4) to determine whether neonatal whisker removal, which deafferents the cortex, will alter the ontogeny of EAA receptors and 5) to determine whether modification of EAA systems by EAA receptor antagonists will alter the structural reassignment of cells and afferents which normally occurs after deafferentation. EAA receptors will be visualized by in vitro receptor autoradiography and immunocytochemistry. The consequences of EAA antagonists and 5HT neurotoxin treatments and of whisker removal on barrel formation will be assessed in terms of changes in size and cytoarchitecture, in patterns of thalamic and non-thalamic (5-HT) afferents and in the density and distribution of EAA receptors. The developing whisker to barrel pathway will serve as a model for examining the role of EAAs in the reorganizational changes which occur after peripheral injury. Since sensory information from the peripheriphery is likely conveyed by EAAs, the characterization of the role of EAA receptors in the establishment of peripheral maps in the cortex is potentially clinically important. By understanding the neurotransmitter control of map formation, it may be possible to design strategies to enhance recovery after injury.

这项研究的长期目标是了解 兴奋性氨基酸递质（EAAs）在皮层形态发生中的作用 和可塑性。 介导EAA作用的受体是 存在于发育中的大脑中，并已被证明在 学习和记忆模型以及发育可塑性。 的 拟议的实验将检查EAA受体在 正常发育的啮齿动物桶场皮层和他们的作用， 新生儿外周神经损伤后发生的皮质结构重新分配 传入神经阻滞 具体目标是：1）描述个体发育 EAA受体在触须（外周输入）到桶（皮质） 途径，2）以确定是否由新生儿引起的EAA的变化 给予EAA受体拮抗剂将改变桶的形成， 3)以确定新生儿给予肾上腺素能 神经毒素，PCA，延迟EAA受体表达的发展， 触须到桶的通路，4）确定新生儿触须是否 去除皮层的传入神经，将改变EAA的个体发育 受体和5）以确定是否修饰EAA系统的EAA 受体拮抗剂将改变细胞的结构再分配， 通常发生在传入神经阻滞后的传入神经。 EAA受体 将通过体外受体放射自显影术可视化， 免疫细胞化学 EAA拮抗剂和5 HT的后果 神经毒素治疗和晶须去除对桶的形成将是 根据大小和细胞结构的变化， 丘脑和非丘脑（5-HT）传入神经的密度和 EAA受体的分布。 发展中的晶须到桶的途径将作为一个模型， 研究EAA在重组变革中的作用， 周围损伤后。 因为来自大脑的感官信息 外围化很可能是由EAA传达的， EAA受体在建立外周地图中的作用 皮质具有潜在的临床重要性。 通过了解 神经递质控制地图的形成，这可能是可能的设计 加强受伤后恢复的策略。