TRANSNEURONAL SIGNALS FOR AFFERENT REGULATION

用于传入调节的跨神经元信号

基本信息

批准号：
6175015
负责人：
RICHARD L. HYSON
金额：
$ 11.69万
依托单位：
FLORIDA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-09-01 至 2001-04-30
项目状态：
已结题

项目摘要

Adequate understanding of the central auditory system requires characterization of the neurochemical communication between cells. It is well known that afferent neurons release neurotransmitters that regulate the electrical activity of postsynaptic cells. Afferent input, however, also regulates the metabolic activity of postsynaptic neurons and is crucial for cell survival. This proposal investigates the signals regulating the electrical and metabolic activity of neurons. The model system used for these studies is the brain stem auditory system of the chick. Second-order neurons in nucleus magnocellularis (NM, the cochlear nucleus) receive their sole excitatory input from the ipsilateral auditory nerve. Elimination of auditory nerve activity results in death and atrophy of NM neurons. Within hours after eliminating auditory nerve activity, changes in metabolism (e.g., protein synthesis) in NM neurons are observed. These effects of deafferentation are reversible if afferent activity to the neuron is restored and these effects of deafferentation are not observed in adult birds. The necessary signals for maintaining and rescuing neurons are currently unknown. The proposed experiments use a variety of methods to investigate the signals regulating the electrical and metabolic activity of NM neurons. Many of these experiments will examine age-related changes in chickens ranging from embryonic to adult ages. Regulation of electrical activity will be investigated physiologically using an in vitro brain slice preparation of the auditory system. A particular emphasis will be placed on the inhibitory neurotransmitter, GABA. Application of GABA has been shown to produce an unusual electrophysiological response in this system. GABA receptors will also be examined anatomically using both receptor binding and in situ hybridization techniques. Metabotropic glutamate receptors (those linked to second messenger systems) will also be examined. Biochemical assays will determine the types of metabotropic receptors present and their pharmacological profile. Physiological experiments using the slice preparation will determine if this receptor also influences the electrical activity of the neuron. Metabolic regulation of Nm neurons will be investigated by assaying changes in protein synthesis and immunolabeling with a ribosome-specific antibody. Unilateral stimulation of the auditory nerve in vitro has been shown to produce metabolic changes similar to those observed in vivo. Application of specific agonists and antagonists will determine the relative roles of different types of excitatory amino acid receptors in transneuronal metabolic regulation. In summary, these experiments will investigate both electrophysiological and metabolic influences of neurotransmitter systems in the brain stem auditory system. These experiments will provide normative data on neurotransmitter receptors and identify receptors that may be involved in the regulation of neuronal metabolism.

对中央听觉系统的充分理解需要细胞之间神经化学通信的表征。这是众所周知，传入神经元释放调节的神经递质突触后细胞的电活动。但是，传入输入，还调节突触后神经元的代谢活性，IS 对于细胞存活至关重要。该提案调查了信号调节神经元的电和代谢活性。模型这些研究使用的系统是脑干的听觉系统小鸡。核细胞核中的二阶神经元（NM，人工耳蜗核）从同侧听到他们的唯一兴奋性输入神经。消除听觉神经活动会导致死亡和 NM神经元的萎缩。消除听觉神经后的几个小时活性，NM神经元中新陈代谢的变化（例如蛋白质合成）观察到。如果传播的话，剥离的这些影响是可逆的恢复了对神经元的活性，并且这些效果的影响在成年鸟类中未观察到。维护的必要信号目前尚不清楚救援神经元。提出的实验使用多种方法来研究信号调节NM神经元的电和代谢活性。这些实验中的许多将检查鸡与年龄相关的变化从胚胎到成人年龄。电活动的调节将使用体外脑切片对生理进行研究准备听觉系统。将放置一个特别的重点在抑制性神经递质上，GABA。 GABA的应用已经显示在该系统中产生异常的电生理反应。 GABA受体也将使用两个受体进行解剖检查结合和原位杂交技术。代谢性谷氨酸受体（链接到第二信使系统的受体）也将是检查。生化测定将确定代谢性的类型受体及其药理特征。生理使用切片制备的实验将确定该受体是否还影响神经元的电活动。代谢 NM神经元的调节将通过测定变化来研究蛋白质合成和核糖体特异性抗体的免疫标记。在体外对听觉神经的单侧刺激已显示为产生类似于体内观察到的代谢变化。应用特定的激动剂和拮抗剂将确定跨神经元中不同类型的兴奋性氨基酸受体代谢调节。总而言之，这些实验将研究两者神经递质系统的电生理和代谢影响在脑干听觉系统中。这些实验将提供关于神经递质受体的规范数据，并鉴定受体可能参与了神经元代谢的调节。