EXPERIENCE AND THE NEUROCHEMISTRY OF THE SYNAPSE

神经系统对环境变化的适应能力 环境对动物的生存至关重要。但有一个例外 感觉神经，它接收环境的信息 直接地，大多数神经细胞只是间接地接受这种信息， 通过改变他们的突触和体液输入。它是一种能力 神经元对这些输入的变化做出反应，最终 产生许多必要的行为和生理适应 生死存亡。拟议的研究主要涉及在 参与突触功能的两类蛋白质： 调节神经递质的生物合成及其参与的蛋白质 神经递质作用。在对这些问题的研究中发展的方法 神经节将用于研究中枢尼古丁受体。以前的工作 证明除了乙酰胆碱，节前颈动脉 交感神经元释放第二种神经递质。它还建立了 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：(一)研究 多肽对TH活性的急性调节机制 分泌素家族，(2)确定这些多肽是否 颈上神经节的神经递质，(3)研究 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 交感神经元胞体，(4)比较刺激特性 所需资源的数量急剧增加，而长期增长 活性，(5)用F毒素(一种蛇毒神经毒素)研究 神经节细胞烟碱受体的调节，以及(6)确定 毒素F也是表征神经元性烟碱的有用配体 中枢神经系统中的受体。这些研究应该澄清 参与神经系统发育的机制及其与 在成人生活中，无论是在正常情况下还是在 各种神经和精神障碍。

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.