TRANSNEURONAL SIGNALS FOR AFFERENT REGULATION

用于传入调节的跨神经元信号

• 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
• 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/6175015
• 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 细胞间神经化学通讯的特征。它是 众所周知，传入神经元释放神经递质，调节 突触后细胞的电活动。然而，传入输入， 也调节突触后神经元和IS的代谢活动 对细胞的生存至关重要。这份提案调查了这些信号 调节神经元的电活动和代谢活动。模型 用于这些研究的系统是脑干听觉系统 小鸡。耳蜗大细胞核(NM)内的二级神经元 核团)接受来自同侧听觉的唯一兴奋性输入 很有胆量。消除听神经活动会导致死亡和 NM神经元萎缩。在去除听神经后的几个小时内 NM神经元的活动、代谢变化(如蛋白质合成) 都被观察到。如果传入，这些去传入的影响是可逆的。 神经元的活动恢复，去传入的这些效应 在成年鸟类身上没有观察到。维持的必要信号 而拯救神经元目前尚不清楚。 拟议的实验使用了各种方法来研究 调节NM神经元的电活动和代谢活动的信号。 其中许多实验将检验鸡的年龄相关变化。 从胚胎年龄到成年年龄不等。对电力活动的监管 将使用体外脑片进行生理学研究 准备好听觉系统。我们将特别强调 抑制神经递质GABA。GABA的应用已被 在这个系统中产生不寻常的电生理反应。 还将使用这两种受体对GABA受体进行解剖检查 结合和原位杂交技术。代谢型谷氨酸 受体(那些连接到第二信使系统的受体)也将 检查过了。生化分析将确定代谢性的类型 受体的存在及其药理学特征。生理学 使用切片制剂的实验将确定该受体是否 也会影响神经元的电活动。新陈代谢 对Nm神经元的调节将通过分析 蛋白质合成和核糖体特异性抗体免疫标记。 体外单侧刺激听神经已被证明 产生与体内观察到的代谢变化类似的变化。应用 将决定特定激动剂和拮抗剂的相对作用 跨神经元兴奋性氨基酸受体的不同类型 代谢调节。总而言之，这些实验将调查这两个 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标准数据，并识别 可能参与了神经元代谢的调节。