EXPERIENCE AND NEUROCHEMISTRY OF THE SYNAPSE

神经系统适应动物体内环境变化的能力。 环境是生存所必需的。这样的环境变化是 在单个神经元水平上主要通过改变 细胞的神经和体液输入。这项建议的重点是影响 突触神经化学的两个方面的这种变化： 神经递质的生物合成及其受体的生物合成 关于发射机的综合，重点介绍了影响发射机综合的因素 既调节递质表型的表达又调节 发射机合成速率的调制。建议的实验是 主要是为了研究神经活动增加的影响 以及暴露于肾上腺类固醇的增加。所选择的模型系统 这些研究是对颈上神经节的大量研究 关于它的解剖学、生物化学和 药理学。在这一领域以前的研究中，人们的注意力集中在 仅见于上节节前和节后神经元 颈神经节。拟议研究的一个关键方面是审查， 此外，非神经细胞在这些调控过程中的作用。 利用了神经节可以很容易地在体内研究的事实， 在外植体培养和分离的细胞培养中。预付款， 尤其是在分子生物学方面，大大增加了工具 可用于此类研究。在本提案中，核酸和 将使用免疫探针来测量 递质合成酶、神经肽和受体都在 M RNA和蛋白水平。该提案的六个具体目标是 如下：(L)研究节前神经节的肽能表型 支配颈上神经节的交感神经元(2)至 检测神经活动增加对血管内皮生长因子表达的影响 该神经节节后神经元中的多肽，(3)测定 节前神经活动增强是否导致兴奋 和/或卫星胶质细胞的增殖，(4)确定 交感神经节中的卫星胶质细胞参与了 递质合成的跨突触或体液调节，(5)至 确定已知的分化因素是否影响表达 交感神经元发育中的递质表型也会影响 成人递质合成的调节，以及(6)研究 神经和体液因素在调控基因表达中的作用 神经节细胞烟碱受体。这项研究的长期目标是 是为了了解潜在的分子和细胞机制 神经化学可塑性。拟议的研究应该阐明机制。 参与神经系统的发育和修改 在成人生活中，无论是在正常情况下还是在各种情况下 神经和精神障碍。临床上，结果应该是 尤其与我们对 神经系统对这样的神经活动增加的反应 由压力、癫痫和某些类型的高血压引起。

The ability of the nervous system to adapt to changes in an animal's environment is essential for survival. Such environmental changes are detected at the level of the single neuron primarily through changes in the cell's neural and humoral inputs. This proposal focuses on the effects of such changes on two aspects of synaptic neurochemistry: the biosynthesis of neurotransmitters and the biosynthesis of their receptors. With regard to transmitter synthesis, emphasis is placed on the factors that regulate both the expression of transmitter phenotypes and the modulation of transmitter synthesis rates. The proposed experiments are designed primarily to investigate the effects of increased nerve activity and of increased exposure to adrenal steroids. The model system chosen for these studies is the superior cervical ganglion, for which a large amount of information is available on its anatomy, biochemistry, and pharmacology. In previous studies in this area, attention has focused solely on the preganglionic and postganglionic neurons in the superior cervical ganglion. One key aspect of the proposed studies is to examine, in addition, the role of non-neuronal cells in these regulatory processes. Use is made of the fact that the ganglion can be readily studied in vivo, in explant cultures and in dissociated cell cultures. Advances, particularly in molecular biology, have greatly increased the tools available for such studies. In the present proposal, both nucleic acid and immunological probes will be used for measuring the expression of transmitter-synthesizing enzymes, neuropeptides and receptors both at the mRNA and protein level. The proposal's six specific aims are as follows:(l) to examine the peptidergic phenotype of preganglionic sympathetic neurons innervating the superior cervical ganglion (2) to examine the effects of increased nerve activity on the expression of peptides in postganglionic neurons in this ganglion, (3) to determine whether increased preganglionic nerve activity leads to the activation and/or proliferation of satellite glial cells, (4) to determine whether satellite glial cells in sympathetic ganglia are involved in the transsynaptic or humoral regulation of transmitter synthesis, (5) to determine whether differentiation factors known to affect the expression of transmitter phenotype in developing sympathetic neurons also affect the regulation of transmitter synthesis in the adult, and (6) to investigate the role of neural and humoral factors in regulating the expression of ganglionic nicotinic receptors. The long-term objective of this research is to understand the molecular and cellular mechanisms underlying neurochemical plasticity. The proposed 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. Clinically, the results should be particularly relevant to our understanding of changes that occur in the nervous system in response to increased nerve activity such as that produced by stress, epilepsy, and certain kinds of hypertension.