ONTOGENY OF COCHLEAR NUCLEUS RESPONSES TO AMINO ACIDS

拟议研究的广泛、长期目标是 神经元的神经生理学和神经药理学方面 耳蜗核复合体的发育。这项研究是 一个更广泛的目标，就是开发一个全面的 支持生物医学研究的哺乳动物听觉发育 旨在确定环境危害对环境的影响 人类听觉功能的发展，以及人类听觉功能的发展 设计用于改善先天和环境的药物 诱发听觉病理学。基于先前研究的结果， 有几个假设将在拟议的实验中得到检验：(1)关于 根据已知的神经支配时间进程，认为兴奋性的发展 谷氨酸能膜受体辅助的功能先于 功能性GABA和甘氨酸介导的抑制作用的发展，(2) 外部影响(耳蜗、其他神经网络等)，而不是 CN神经元的固有特性，是观察到的反应不成熟的基础 以及(3)突触前元素的发育速度限制 CN中的“功能性突触发生”。与频率相关的方面 GABA和甘氨酸介导的CN神经元抑制作用的研究进展 第一次在听觉结构中被直接研究，在 以前从未研究过的神经元群体。此外，与以下内容相关的更改 将研究内源氨基酸的浓度和功能。 在发育阶段表现出广泛的突触形成和 神经营养活性。为了达到规定的目标，进行实验 涉及标准的单个神经元电生理学 将进行微离子电泳术和标准生理学 并且将利用药理学程序(即，当前/或 剂量/反应曲线分析，氨基酸对放电率的调节。 声级功能，声音诱发的时间放电模式， 等)来描述这个脑干核团中的神经元。此外，高 高效液相色谱与电化学联用 将使用检测方法来确定GABA和 甘氨酸在整个出生后发育的特定CN区域中可用。 他们的浓度将被分析与电生理和 药理学结果，特别是在实验范例方面 旨在阐明我们对发展的相关性的理解 与内源性配体作用相关的变化。建议的结果 研究将提供对某些关键分子事件的确切理解 潜在的中枢听觉系统发育。

The broad, long-term objective of the proposed research is to characterize the neurophysiological and neuropharmacological aspects of neuronal development in the cochlear nuclear (CN) complex. This research is part of an even broader objective, which is to develop a comprehensive model of mammalian auditory development that will support biomedical research designed to determine the influence of environmental hazards on the development of auditory function in humans, as well as the development of pharmaceuticals engineered to ameliorate congenital and environmentally induced auditory pathology. Based upon results from previous research, several hypotheses are to be tested in proposed experiments: (1) on the basis of known innervation time courses, that the development of excitatory function subserved via glutamatergic membrane receptors precedes the development of functional GABA and glycine mediated inhibition, (2) that extrinsic influences (cochlear, other neural networks, etc.),, rather than intrinsic properties of CN neurons, underlie observed response immaturities and (3) that the development of presynaptic elements rate limits 'functional synaptogenesis' in CN. The frequency-dependent aspects of the development of GABA and glycine mediated inhibition among CN neurons will be studied directly for the first time in an auditory structure, among a population of neurons never before studied. Also, changes associated with concentrations and function of endogenous amino acids will be studied during developmental periods exhibiting extensive synaptogenic and neurotrophic activity. To achieve the stated objectives, experiments involving standard single neuron electrophysiology in combination with microionophoresis procedures will be performed and standard physiological and pharmacological procedures will be utilized (i.e., current/or dose/response curve analyses, amino acid modulation of discharge rate vs. sound level functions, acoustically-evoked temporal discharge patterns, etc.) to characterize neurons in this brainstem nucleus. In addition, high performance liquid chromatography (HPLC) and combined electrochemical detection methods will be used to determine the concentrations of GABA and glycine available in specific CN regions throughout postnatal development. Their concentrations will be analyzed in relation to electrophysiology and pharmacology results, particularly with regard to experimental paradigms designed to illuminate our understanding of the relevance of developmental changes associated with endogenous ligand actions. Results of proposed research will provide a firm understanding of certain key molecular events underlying central auditory system development.