EXPERIENCE AND THE NEUROCHEMISTRY OF THE SYNAPSE

经验和突触的神经化学

• 批准号: 3394942
• 负责人: RICHARD E ZIGMOND
• 金额: $ 20.95万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-05-01 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3394942
• 关键词: adrenergic agents; autonomic nervous system; autoradiography; bungarotoxins; chromaffin cells; cyclic AMP; enzyme mechanism; ganglions; glucocorticoids; high performance liquid chromatography; immunofluorescence technique; ion transport; laboratory rat; membrane permeability; nerve endings; neural information processing; neural plasticity; neurochemistry; neurogenesis; neuropeptides; neuropharmacology; neurotoxins; neurotransmitter biosynthesis; nicotinic receptors; norepinephrine; organ culture; peripheral nervous system; pituitary adrenal axis; radioimmunoassay; radiotracer; sympathetic nervous system; synapses; tissue /cell culture; tyrosine 3 monooxygenase

The adaptability of the nervous system in response to changes in the environment is essential for the survival of an animal. With the exception of sensory nerves, which receive information about the environment directly, most nerve cells receive such information only indirectly, through changes in their synaptic and humoral inputs. It is the ability of neurons to change in response to changes in these inputs which ultimately produces many of the behavioral and physiological adaptations necessary for survival. The proposed research deals primarily with adaptive changes in two classes of proteins involved in synaptic function: the enzymes which regulate neurotransmitter biosynthesis and the proteins involved in neurotransmitter action. The approaches developed in studies on these ganglia will be used to study central nicotinic receptors. Previous work demonstrated that in addition to acetylcholine, preganglionic cervical sympathetic neurons release a second neurotransmitter. It also established that certain neuropeptides alter the activity of tyrosine hydroyxlase (TH), the enzyme which catalyzes the rate-limiting step in catecholamine biosynthesis. Our proposal has six specific aims: (1) to study the mechanisms involved in the acute regulation of TH activity by peptides of the secretin family, (2) to determine whether these peptides are neurotransmitters in the superior cervical ganglion, (3) to investigate whether cholinergic and peptidergic agonists stimulate TH activity in sympathetic nerve terminals and in adrenal chromaffin cells as they do in sympathetic neuron cell bodies, (4) to compare the stimulus properties required for the elicitation of an acute versus a long-term increase in TH activity, (5) to use toxin F (a snake venon neurotoxin) to study the regulation of ganglionic nicotinic receptors, and (6) to determine whether toxin F is also a useful ligand for characterizing neuronal nicotinic receptors in the central nervous system. These studies should elucidate mechanisms involved in the development of the nervous system and in its modification during adult life, both under normal conditions and in a variety of neurological and psychiatric disorders.

神经系统对环境变化的适应性 环境对于动物的生存至关重要。 例外 感觉神经，接收有关环境的信息 大多数神经细胞只是间接地直接接收此类信息， 通过突触和体液输入的变化。 它的能力是 神经元会响应这些输入的变化而变化，最终 产生许多必要的行为和生理适应 生存。 拟议的研究主要涉及适应性变化 参与突触功能的两类蛋白质： 调节神经递质生物合成和参与的蛋白质 神经递质的作用。 这些研究中开发的方法 神经节将用于研究中枢烟碱受体。 以前的工作 证明除了乙酰胆碱外，节前颈椎 交感神经元释放第二种神经递质。 还设立了 某些神经肽改变酪氨酸水解酶（TH）的活性， 催化儿茶酚胺限速步骤的酶 生物合成。 我们的建议有六个具体目标：（1）研究 肽对 TH 活性的急性调节机制 促胰液素家族，(2) 确定这些肽是否是 颈上神经节的神经递质，（3）调查 胆碱能和肽能激动剂是否刺激 TH 活性 交感神经末梢和肾上腺嗜铬细胞 交感神经元细胞体，（4）比较刺激特性 引起 TH 急性与长期增加所需的量 活性，（5）使用毒素F（一种蛇毒神经毒素）来研究 神经节烟碱受体的调节，以及（6）确定是否 毒素 F 也是表征神经元烟碱的有用配体 中枢神经系统中的受体。 这些研究应该阐明 参与神经系统发育的机制及其 成人生活中的改变，无论是在正常条件下还是在特定条件下 各种神经和精神疾病。