EXPERIENCE AND NEUROCHEMISTRY OF THE SYNAPSE

神经系统适应动物神经系统变化的能力 环境对生存至关重要。这种环境变化是 在单个神经元的水平上检测到，主要是通过 细胞的神经和体液输入。这一建议的重点是影响 这种变化对突触神经化学的两个方面： 神经递质的生物合成及其受体的生物合成。 关于发射机综合，重点放在因素 调节递质表型的表达， 发射机合成速率的调制。建议的实验是 主要用于研究神经活动增加 以及肾上腺类固醇的增加。选择的模型系统 这些研究是上级颈神经节， 关于它的解剖学、生物化学和 药理学在这一领域的以往研究中， 仅在上级的节前和节后神经元上 颈神经节拟议研究的一个关键方面是审查， 此外，非神经元细胞在这些调节过程中的作用。 利用的事实是，神经节可以很容易地在体内研究， 在外植体培养物和分离的细胞培养物中。预付款， 尤其是在分子生物学领域， 可用于此类研究。在本发明中，核酸和 免疫学探针将用于测量 神经递质合成酶、神经肽和受体， mRNA和蛋白水平。该提案的六个具体目标如下： （1）检测节前神经节细胞的肽能表型， 支配上级颈神经节的交感神经元（2）， 检查增加的神经活动对表达的影响， 肽在节后神经元在这个神经节，（3）以确定 增加的节前神经活动是否导致激活 和/或卫星神经胶质细胞的增殖，（4）以确定是否 交感神经节中的卫星神经胶质细胞参与了 递质合成的跨突触或体液调节，（5） 确定已知影响表达的分化因子是否 在交感神经元发育过程中， 调节成人的递质合成，以及（6）调查 神经和体液因素在调节表达中的作用 神经节烟碱受体这项研究的长期目标是 是了解其分子和细胞机制 神经化学可塑性拟议的研究应阐明机制 参与神经系统的发育和改造 在成年生活中，无论是在正常条件下， 神经和精神疾病。临床上，结果应该是 特别是与我们对发生在地球上的变化的理解有关， 神经系统对增加的神经活动的反应，如 由压力癫痫和某些高血压引起

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.