AMINO ACID RECEPTORS IN NEONATAL TRIGEMINAL NEURONS

新生儿三叉神经元中的氨基酸受体

• 批准号: 2503447
• 负责人: JACK E TURMAN
• 金额: $ 4.04万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-15 至 2000-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2503447
• 关键词: AMPA receptors; GABA receptor; NMDA receptors; autoradiography; developmental neurobiology; glutamate decarboxylase; glutamate receptor; immunocytochemistry; innervation; laboratory rat; mesencephalon; monoclonal antibody; motor neurons; neuroanatomy; neurochemistry; neurons; newborn animals; protein structure; receptor expression; trigeminal nerve

During development mammals demonstrate a transition from suckling to chewing behavior for the ingestion of nutrients. These behaviors and the transition between them are essential for normal development and survival. Two critical components comprising the neural circuitry responsible for oral-motor behaviors are trigeminal motoneurons and mesencephalic trigeminal neurons. Insight regarding oral-motor development will be gained by correlating the development of terminals innervating trigeminal motoneurons and mesencephalic trigeminal neurons with the development of neurotransmitter receptor complexes utilized to modulate the activity of these neurons. This study will be the first to characterize oral-motor development using chemical neuroanatomical techniques. This will be accomplished by correlating changes in the glutamatergic and GABAergic innervation of trigeminal motoneurons and mesencephalic trigeminal neurons with the ontogeny of NMDA, AMPA, and GABAa receptors in these neurons during early postnatal development. Three different experimental protocols will be performed on rats at postnatal day 1, 5, 15, and 25 as these ages represent critical periods in oral-motor development. In the first set of experiments, a polyclonal antibody against glutamate and a polyclonal antibody against glutamate decarboxylase (GAD) will be used to label glutamatergic and GABAergic terminals throughout the trigeminal motor nucleus and mesencephalic trigeminal nucleus. In the second set of experiments, receptor immunohistochemistry using antibodies against NMDA, AMPA, and GABAa subunits will be used to describe the temporal and spatial expression of NMDA, AMPA, and GABAa receptors in trigeminal motoneurons and mesencephalic trigeminal neurons. Finally, quantitative receptor autoradiography using [3H]MK-801, [3H]AMPA, and [3H]muscimol will be used to determine density changes of NMDA, AMPA and GABAa receptors respectively. The results from these studies will provide insight into the role of glutamate and GABA in controlling neonatal trigeminal motoneuron and mesencephalic trigeminal neuron activity in order to further understand the development and function of early oral-motor circuits.

在发育过程中，哺乳动物表现出从哺乳到 咀嚼行为以摄取营养。 这些行为和 它们之间过渡对正常发展至关重要， 生存 神经回路的两个关键组成部分 负责口腔运动行为的是三叉神经运动神经元， 中脑三叉神经元 关于口腔运动的见解 通过与终端的发展相关联， 支配三叉神经运动神经元和中脑三叉神经元 随着神经递质受体复合物的发展， 来调节这些神经元的活动。 本研究将 第一个用化学物质来描述口腔运动发育的特征 神经解剖学技术 这将通过关联 三叉神经的多巴胺能和GABA能神经支配的变化 运动神经元和中脑三叉神经元的个体发育 出生后早期这些神经元中的NMDA、AMPA和GABA a受体 发展将进行三种不同的实验方案 出生后第1、5、15和25天的大鼠，这些年龄代表 口腔运动发育的关键时期。 的第一集合中 实验中，针对谷氨酸的多克隆抗体和多克隆抗体， 谷氨酸脱羧酶（GAD）抗体将用于标记 三叉神经运动中的GABA能和多巴胺能终末 核和三叉神经中脑核。 的第二集合中 实验，受体免疫组织化学使用抗体， NMDA、AMPA和GABAa亚基将用于描述时间上的变化。 NMDA、AMPA和GABAa受体在三叉神经中的空间表达 运动神经元和中脑三叉神经元。 最后， 使用[3 H]MK-801、[3 H]AMPA和 [3 H]蝇蕈醇将用于测定NMDA、AMPA的密度变化 和GABAa受体。 这些研究的结果将 深入了解谷氨酸和GABA在控制 新生三叉神经运动神经元和中脑三叉神经元 活动，以进一步了解发展和功能 早期的口腔运动回路