ONTOGENY OF COCHLEAR NUCLEUS RESPONSES TO AMINO ACIDS

发育中的听觉神经元的反应特性表明， 在出生后早期发育过程中，功能可能不成熟。 响应 潜伏期延长，暂时放电模式不显示 特征性成人样模式，输入/输出的动态范围 功能大大减少，放电同步（即， 锁相）被减弱。 为了确定不成熟的 突触对这些发展中的反应模式，我们建议研究 神经元的电生理和药理学发育 耳蜗背核（DCN）和后腹核（PVCN） 小猫 有待检验的总体假设是， 从年轻动物记录的DCN和PVCN神经元的特性是 是不成熟的突触机制的结果 突触传递将是 通过检查神经元对声音的反应来进行电生理学评估 在整个产后发育过程中的刺激。 我们将评估 突触后受体功能的年龄之前， 引起声诱发响应（例如，从出生到5-7岁 出生后天），通过检查兴奋性（谷氨酸和 天冬氨酸）和抑制（γ-氨基丁酸（GABA）和甘氨酸） 氨基酸微电泳施加到DCN和PVCN神经元上。 受体特异性的氨基酸介导的兴奋或抑制将 通过同时给予特定受体进行评价 拮抗剂在氨基酸应用期间和在声刺激期间。 在整个开发过程中，我们将确定假定的氨基的影响， 酸性神经递质及其拮抗剂对放电率、放电 同步，响应阈值，频率限制 反应性，以及整个反应过程中的时间放电模式 CN神经元区。 最后，我们假设， 受体活化（即，达到最大效应的时间） 给药，以及出院活动的时间过程 在微离子电渗停止后终止，在出生后 开发，并且该过程的表征可用于 绘制CN内突触传递的成熟图。 这些研究 代表了对化学品发展方面的初步调查， 听觉系统的神经传递，这是重要的第一步， 在开发治疗，药理学策略，旨在 治疗可能以神经化学异常为特征的听力异常 不平衡

Response properties of developing auditory neurons suggest that synaptic function may be immature during early postnatal development. Response latencies are prolonged, temporal discharge patterns do not display the characteristic adult-like patterns, dynamic ranges of input/output functions are greatly reduced, and discharge synchronization (i.e., phase-locking) is diminished. To determine the contribution that immature synapses make to these developing response patterns, we propose to study the electrophysiological and pharmacological development of neurons within the dorsal (DCN) and posteroventral (PVCN) cochlear nuclei (CN) of kittens. The overall hypothesis to be tested is that immature response properties of DCN and PVCN neurons recorded from young animals are the result of immature synaptic mechanisms. Synaptic transmission will be assessed electrophysiologically by examining neuronal responses to acoustic stimulation throughout postnatal development. We will evaluate postsynaptic receptor function prior to the age at which acoustically-evoked responses are elicited (e.g., between birth and 5-7 postnatal days), by examining the effects of excitatory (glutamate and aspartate) and inhibitory (gamma-aminobutyric acid (GABA) and glycine) amino acids microiontophoretically applied onto DCN and PVCN neurons. Receptor specificity of amino acid-mediated excitation or inhibition will be evaluated by the simultaneous administration of specific receptor antagonists during amino acid application and during acoustic stimulation. Throughout development, we will determine the effects of the putative amino acid neurotransmitters and their antagonists on discharge rate, discharge synchronization, response thresholds, the frequency limits of responsiveness, and on temporal discharge patterns throughout the response area of CN neurons. Finally, we hypothesize that the time course of receptor activation (i.e., time to maximum effect) following amino acid administration, and the time course over which discharge activity is terminated after cessation of microiontophoresis, varies during postnatal development, and that the characterization of that process can be used to map the maturation of synaptic transmission within the CN. These studies represent an initial investigation of developmental aspects of chemical neurotransmission in the auditory system, which is an important first step in the development of therapeutic, pharmacologic strategies aimed at the treatment of hearing anomalies that may be characterized by neurochemical imbalance.