TRANSNEURONAL SIGNALS FOR AFFERENT REGULATION

用于传入调节的跨神经元信号

• 批准号: 2909879
• 负责人: RICHARD L. HYSON
• 金额: $ 11.24万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/2909879
• 关键词: GABA receptor; afferent nerve; aging; auditory pathways; bicarbonates; bicuculline; brain stem; chickens; cyclic AMP; gamma aminobutyrate; glutamate receptor; in situ hybridization; neural transmission; neuropharmacology; phosphatidylinositols; picrotoxin; protein structure function; receptor binding; synapses

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.

对中枢听觉系统的充分了解需要 表征细胞之间的神经化学通讯。 是 众所周知，传入神经元释放神经递质， 突触后细胞的电活动 然而，传入输入， 还调节突触后神经元的代谢活动， 对细胞存活至关重要。 该提案调查了 调节神经元的电和代谢活动。 模型 用于这些研究的系统是脑干听觉系统， 小妞 大细胞核（NM，耳蜗）中的二级神经元 核）从同侧听觉接受唯一的兴奋性输入 神经。 听觉神经活动的消失会导致死亡， NM神经元萎缩。 听神经消失后数小时内 活性，代谢的变化（例如，蛋白质合成）在NM神经元 被观察到。 这些影响的传入是可逆的，如果传入 神经元的活动得到恢复， 在成年鸟类中没有观察到。 维护的必要信号 和拯救神经元的方法目前还不清楚。 拟议的实验使用各种方法来研究 调节NM神经元的电和代谢活动的信号。 许多这些实验将检查鸡的年龄相关的变化 从胚胎期到成年期。 电活动调节 将使用体外脑切片进行生理学研究 听觉系统的准备。 将特别强调 抑制性神经递质GABA GABA的应用 显示在这个系统中产生不寻常的电生理反应。 GABA受体也将在解剖学上使用两种受体进行检查。 结合和原位杂交技术。 代谢型谷氨酸 受体（与第二信使系统相连的受体）也将被 考察 生化分析将确定代谢型 受体及其药理学特征。 生理 使用切片制备的实验将确定这种受体是否 也会影响神经元的电活动。 代谢 Nm神经元的调节将通过测定 蛋白质合成和用核糖体特异性抗体进行免疫标记。 体外听神经的单侧刺激已被证明可以 产生类似于体内观察到的代谢变化。 应用 特异性激动剂和拮抗剂的作用将决定 不同类型的兴奋性氨基酸受体在跨神经元 代谢调节 总之，这些实验将研究 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 神经递质受体的标准数据，并确定受体， 可能参与神经元代谢的调节。