CODING IN AUDITORY NEURONS: EFFECTS OF AMINO ACIDS

神经异常，包括感受性失语、神经性老年性耳聋 听觉知觉障碍可能与神经化学缺陷有关。这 一项提案研究了神经递质在声学编码中的作用 信息，目标是确定和描述可能的 神经递质丢失对正常衰老和病理的影响 沟通障碍。拟议的研究将评估神经递质 耳蜗核在介导突触传递中的作用 和下丘(IC)。离子导入的药理作用 应用药物将使用几种不同的声学范例进行检查。 这个实验室已经成功地识别了神经递质和它们的 在几个关键的脑干听觉回路上发挥作用 神经生理学和神经药理学技术在 目前的研究。耳蜗前腹核(AVCN)的几个研究 氨基酸γ-氨基丁酸(GABA)和甘氨酸的支持作用 作为抑制性神经递质。模仿测试(行为同一性)和 使用选择性受体激动剂和 突触释放化合物的拮抗剂将：1)检查 GABAA、GABAB和甘氨酸I类相关化合物的区别作用 离子电泳法应用于三种AVCN响应类型。令人兴奋 初步结果表明，对于某些反应类型，近场循环和 依赖于速率的饱和反应而不是侧向抑制可能是 部分由这些神经递质控制。相当多的证据 支持兴奋性氨基酸(EAA)神经递质在 CN内的听神经突触。改进对受体介导的检查 现在有了新的、更有选择性的EAA，CN中的声音诱发激发成为可能 受体拮抗剂。2-氨基-5-膦-戊酸(AP5)，a 选择性N-甲基-D-天冬氨酸(NMDA)受体拮抗剂 对新的，选择性的，非NMDA受体拮抗剂6，7-二硝基喹恶啉- 在CN中诱发反应。大鼠的IC经历了显著的年龄相关 GABA丢失(11，12，43)。青年Fischer-344的离子电泳学研究 (F-344)大鼠将扩展先前关于GABA在 在IC中处理双耳和强度信息。在确认后 GABA在CIC特定声学范式中的作用，生理学研究 老年F-344大鼠将被用来评估与年龄相关的GABA变化 功能。从年轻成年F-344大鼠IC获得的数据将与 在成年栗鼠IC中进行类似的离子导入研究，将重点放在 ON-Low-Low CF神经元的相位敏感性年龄相关性抑制丧失 大鼠IC的功能可能对理解神经学有意义 以失语为特征的男性老年性耳聋 噪声中信号的可理解性和检测能力。

Neurological abnormalities including receptive aphasia, neural presbycusis and auditory perceptual dysfunction may involve neurochemical faults. This proposal examines the role neurotransmitters have in coding acoustic information with the goal of identifying and characterizing possible consequences neurotransmitter loss has on normal aging and pathologic communicative disorders. Proposed studies will evaluate neurotransmitter functions in mediating synaptic transmission in the cochlear nucleus (CN) and inferior colliculus (IC). Pharmacological effects of iontophoretically applied drugs will be examined using several different acoustic paradigms. This laboratory has successfully identified neurotransmitters and their functions at several key brainstem auditory circuits using similar neurophysiological and neuropharmacological techniques proposed in the present study. In anterior ventral cochlear nucleus (AVCN) several studies support roles for amino acids gamma-amino-n-butyric acid (GABA) and glycine as inhibitory neurotransmitters. Tests of mimicry (identity of action) and antagonism (pharmacologic identity) using selective receptor agonist and antagonists of synaptically released compounds will: 1) examine differential effects of GABAA, GABAB and glycine I related compounds iontophoretically applied onto three AVCN response types. Exciting preliminary results indicate that for certain response types, near-CF and rate dependent saturation responses but not lateral inhibition may be partially controlled by these neurotransmitters. Considerable evidence supports a role for excitant amino acid (EAA) neurotransmitters acting at acoustic nerve synapses in CN. Improved examination of receptors mediating sound-evoked excitation in CN is now possible with new, more selective, EAA receptor antagonists. DL-2-amino-5-phosphonovaleric acid (AP5), a selective N-methyl-D-aspartate (NMDA) receptor antagonist, will be compared to the new, selective, non-NMDA receptor antagonist 6,7-dinitroquinoxaline- evoked responses in CN. The rat IC undergoes a significant age-related loss of GABA (11,12,43). Iontophoretic studies in young adult Fischer-344 (F-344) rat will extend previous findings as to the role GABA plays in processing binaural and intensity information in IC. After confirmation of GABA's role in specific acoustic paradigms in CIC, physiological studies in aged F-344 rats will be used to assess age-related changes in GABA function. Data obtained from young adult F-344 rat IC will be compared to a similar iontophoretic study in adult chinchilla IC which will focus on phase sensitivity in on-low CF neurons. Age-related loss of inhibitory function in rat IC may have implications for understanding neural presbycusis in man which is characterized by a loss of speech intelligibility and inability to detect signal in noise.