Post Synaptic Receptors Mediating Eighth Nerve Function

突触后受体介导第八神经功能

• 批准号: 6379599
• 负责人: SHUNDA R IRONS-BROWN
• 金额: $ 2.14万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-25 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6379599
• 关键词: GABA receptor; NMDA receptors; acoustic nerve; action potentials; afferent nerve; bicuculline; chickens; glutamate receptor; neuropharmacology; neurotransmitter antagonist; perilymph; picrotoxin; quinoxalines; vestibular nerve; GABA receptor; NMDA receptors; acoustic nerve; action potentials; afferent nerve; bicuculline; chickens; glutamate receptor; neuropharmacology; neurotransmitter antagonist; perilymph; picrotoxin; quinoxalines; vestibular nerve

DESCRIPTION (from applicant's abstract): The specific aim in the proposed work is to identify post-synaptic receptors mediating the primary afferent response to vestibular and auditory stimulation in the chicken (Gallus domesticus, ages 11 to 14 days old). To do this we have developed a perilymphatic perfusion system for the avian auditory and vestibular end organs. Using vestibular and auditory compound action potentials (VCAP and ACAP respectively), we will test the effects of specific receptor blockers on the activation of vestibular and auditory neurons. The VCAP and ACAP tests will enable the measurement of dose response curves for auditory and vestibular neurons at each drug concentration chosen under otherwise identical physiological conditions. These techniques will be employed to critically test the following hypotheses in the chicken. Hypothesis 1: The primary afferent receptors mediating auditory compound action potentials are glutamate non-NMDA receptors. Hypothesis 2: The primary afferent receptors mediating vestibular compound action potentials are NMDA glutamate and/or GABA receptors. Using perilymphatic perfusion in a well-controlled physiological preparation, the effects of appropriate micromolar (mM) concentrations of drugs will be studied in situ. The effects of six chemical agents on evoked auditory and vestibular activity will be evaluated. To test hypothesis 1, non-NMDA receptor antagonists (6-cyano-7-nitroquinoxaline-2,3- dione [CNQX] and 6,7-dinitroquinoxaline-2,3-dione [DNQX]) will be used. Hypothesis 2 will be tested in two parts: 1) the role of NMDA receptors will be assessed using glutamate NMDA antagonists (D-a-aminoadipic acid [DAA] and D-L-2- amino-5-phosphonovaleric acid [APV]); and 2) response mediation by GABA receptors will be tested using GABA-A receptor antagonists bicuculline and picrotoxin. Significant reduction or blockade of responses in micromolar dose ranges will support the respective hypotheses. The absence of effects at all doses will rule out a critical role for the respective receptor types in the generation of the ACAP and VCAP.

描述（来自申请人的摘要）：拟议工作的具体目的 是识别介导的主要传入反应的突触后受体 到鸡肉的前庭和听觉刺激（Gallus fordayus 11至14天大）。为此，我们开发了一种围绕的灌注 禽听觉和前庭器官的系统。使用前庭和 听觉复合动作电位（分别为VCAP和ACAP），我们将测试 特定受体阻滞剂对前庭和激活的影响 听觉神经元。 VCAP和ACAP测试将实现剂量的测量 每个药物浓度下听觉和前庭神经元的反应曲线 在原本相同的生理条件下选择。这些技术会 被用来严格检验鸡肉中的以下假设。 假设1：介导听觉化合物动作的主要传入受体 电位是谷氨酸非NMDA受体。假设2：主要传入 介导前庭复合作用电位的受体是NMDA谷氨酸 和/或GABA受体。在控制良好 生理准备，适当的微摩尔（MM）的影响 药物的浓度将在原位研究。六种化学的影响 将评估有关诱发听觉和前庭活动的药物。测试 假设1，非NMDA受体拮抗剂（6-Cyano-7-Nitroquinoxaline-2,3-- 将使用Dione [CNQX]和6,7-二硝基喹又2,3-二酮[DNQX]）。 假设2将分为两个部分：1）NMDA受体的作用将是 使用谷氨酸NMDA拮抗剂（D-A-氨基丙酸[DAA]和D-L-2--评估 氨基-5-膦共甲酸[APV]）; 2）GABA的响应调解 受体将使用GABA-A受体拮抗剂双culline和 野毒素。微摩尔剂量的重大减少或阻断反应 范围将支持各自的假设。根本没有效果 剂量将排除相应受体类型的关键作用 ACAP和VCAP的产生。