Post Synaptic Receptors Mediating Eighth Nerve Function

描述（来自申请人的摘要）：拟议工作的具体目标 是识别调节初级传入反应的突触后受体 前庭和听觉刺激的鸡（Gallus arteriticus，年龄 11至14天）。为此，我们开发了一种外淋巴灌注 鸟类听觉和前庭终末器官系统。使用前庭和 听觉复合动作电位（VCAP和ACAP分别），我们将测试 特异性受体阻滞剂对前庭神经元激活的影响， 听觉神经元VCAP和ACAP测试将能够测量剂量 各药物浓度下听觉和前庭神经元的反应曲线 在其他相同的生理条件下选择。这些技术将 用鸡来批判性地检验以下假设。 假设1：初级传入受体介导听觉复合作用 电位是谷氨酸非NMDA受体。假设2：初级传入 介导前庭复合动作电位的受体是NMDA谷氨酸 和/或GABA受体。使用外淋巴灌注在一个控制良好的 生理制剂，适当微摩尔（mM）的影响 将在现场研究药物浓度。六种化学物质的影响 将评估对诱发的听觉和前庭活动的药剂。测试 假设1，非NMDA受体拮抗剂（6-氰基-7-硝基喹喔啉-2，3- 二酮[CNQX]和6，7-二硝基喹喔啉-2，3-二酮[DNQX]）。 假设2将在两个部分中进行检验：1）NMDA受体的作用将是 使用谷氨酸NMDA拮抗剂（D-a-氨基己二酸[DAA]和D-L-2-氨基己二酸[DAA]）进行评估。 氨基-5-磷酸戊酸[APV]）;和2）GABA的反应介导 将使用GABA-A受体拮抗剂荷包牡丹碱和 印防己毒素显著降低或阻断微摩尔剂量的反应 范围将支持各自的假设。完全没有效果 剂量将排除相应受体类型在 ACAP和VCAP的产生。

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.