COORDINATE REGULATION OF COEXISTING NEUROTRANSMITTERS

哺乳动物中枢神经系统中的单个神经元 含有不止一种神经递质。由于环境原因 信号改变神经递质基因的表达，存在 单个神经元内的多个神经递质系统增加 神经元反应的潜在复杂性。因此，我们， 计划研究三种神经递质的协调调节 已知共定位于丘脑腹侧内侧核神经元 小鼠和大鼠的大脑：“经典”的单胺类递质 5-羟色胺(5-羟色胺)、P物质(SP)和 促甲状腺激素释放激素(TRH)。P物质的cDNA探针 和TRH前体激素是可用的。技术的应用 用分子生物学方法研究人类免疫缺陷问题 神经递质的表达将使我们能够检查这些问题 在基因表达水平上。配备了这两种工具 神经药理学和分子生物学，然后，我们计划 确定5-羟色胺水平的药理学改变 影响共定位的多肽神经递质的表达， 以及2)确定观察到的多肽变化 表达是5-羟色胺能改变的结果 神经传递。体内研究将通过研究延长 在器官型组织培养中进行，其中 可以更仔细地控制微环境。

Single neurons in the mammalian central nervous sytem (CNS) contain more than one neurotransmitter. Since environmental signals alter neurotransmitter gene expression, the existence of multiple neurotransmitter systems within single neurons increases the potential complexity of neuronal responses. We, therefore, plan to study the coordinate regulation of three neurotransmitters known to be co-localized in neurons of the ventral medualla of mouse and rat brain: the "classical" monoamine transmitter serotonin (5 - HT), the peptide transmitters substance P (SP) and thyrotropin-releasing hormone (TRH). cDNA probes for the SP and TRH preprohormones are available. The application of molecular biological approaches to the problem of neurotransmitter expression will allow us to examine these issues at the level of gene expression. Armed with the tools of both neuropharmacology and molecular biology, then, we plan 1) to determine whether pharmacological alterations in serotonin levels affect the expression of co-localized peptide neurotransmitters, and 2) determine whether the observed changes in peptide expression are the result of altered serotonergic neurotransmission. Studies in vivo will be extended by studies performed in organotypic tissue culture where the microenvironment can be more carefully controlled.