EXCITATORY AMINO ACIDS AND CORTEX DEVELOPMENT

兴奋性氨基酸和皮质发育

• 批准号: 2267416
• 负责人: Mary E Blue
• 金额: $ 10.33万
• 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/2267416
• 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 兴奋性氨基酸发射器（EAA）在皮质形态发生中播放 和可塑性。 介导EAA动作的受体是 存在于发育中的大脑中，并已被证明在 学习和记忆和发展可塑性的模型。 这 提出的实验将检查EAA受体在 啮齿动物桶田皮质的正常发育及其在 在新生儿周围发生的皮质的结构重新分配 停用。 具体目的是1）表征个体发育 晶须中的EAA受体（外围输入）到枪管（皮质） 途径，2）确定新生儿引起的EAA的变化是否 EAA受体拮抗剂的给药将改变桶形的形成， 3）确定血清素能的新生儿给药是否 神经毒素PCA延迟了EAA受体表达的发展 晶须到枪管途径，4）确定新生儿晶须是否 取消皮层的去除将改变EAA的个体发育 受体和5）确定EAA对EAA系统的修改是否 受体拮抗剂将改变细胞和 通常发生在脱落后的传入。 EAA受体 将通过体外受体放射自显影和 免疫细胞化学。 EAA拮抗剂和5HT的后果 神经毒素治疗和枪管形成的晶须去除将是 根据大小和细胞结构的变化评估 丘脑和非丘脑（5-HT）传入以及密度和 EAA受体的分布。 开发晶须到枪管途径将成为 检查EAA在发生重组变化中的作用 外周损伤后。 由于感官信息来自 外围病可能是由EAA传达的， EAA受体在建立外围图中的作用 皮质在临床上可能很重要。 通过理解 神经递质控制地图形成，可能可以设计 受伤后增强恢复的策略。