Post Synaptic Receptors Mediating Eighth Nerve Function

描述(摘自申请者的摘要)：建议工作的具体目标 是识别介导初级传入反应的突触后受体 对鸡的前庭和听觉刺激(Gallus home ticus，AGE 11至14日龄)。为了做到这一点，我们开发了外淋巴灌流。 鸟类听觉和前庭末梢器官的系统。使用前庭和 听觉复合动作电位(分别为VCAP和ACAP)，我们将测试 特异性受体阻滞剂对前庭神经电活动的影响 听觉神经元。VCAP和ACAP测试将使剂量测量成为可能 听神经元和前庭神经元在不同药物浓度下的反应曲线 在其他相同的生理条件下选择的。这些技术将 被用来在鸡身上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动作 潜在的是谷氨酸非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。外淋巴灌流在控制良好的 生理制剂，适当微摩尔(Mm)的影响 药物浓度将在现场进行研究。六种化学物质的作用 对诱发的听觉和前庭活动的药物将进行评估。为了测试 假设1，非NMDA受体拮抗剂(6-氰基-7-硝基喹恶啉-2，3- 将使用二酮[CNQX]和6，7-二硝基-2，3-二酮[DNQX])。 假设2将分两部分进行检验：1)NMDA受体的作用将是 使用谷氨酸N-甲基-D-天冬氨酸拮抗剂(D-a-氨基己二酸和D-L-2- 氨基-5-膦戊酸[APV])；和2)GABA介导的反应 使用GABA-A受体拮抗剂荷包牡丹碱和荷包牡丹碱来测试受体 印防己毒素。显著降低或阻断微摩尔剂量的反应 Range将支持各自的假设。完全没有效果 剂量将排除各自受体类型在 ACAP和VCAP的生成。

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.