MOLECULAR NEUROBIOLOGY AND DEVELOPMENTAL DISORDERS

这是一个竞争性的续期申请，以继续支持我们的 分子神经生物学和发育障碍的研究项目。的 该计划包括一个行政和科学核心，为五个 主要调查领域。每个区域都有其中心主题， 分子神经生物学在理解发育神经系统中的应用 过程及其规范。5-羟色胺调节与 β-肾上腺素能受体部分检查血清素的调节， β-肾上腺素能受体mRNA和G-蛋白偶联在发育过程中， 以及抗抑郁药和药物对这些受体mRNA的调节 从而改变神经传递这项工作试图了解这些因素 启动和维持受体基因表达。关于酶的部分 调节的重点是激素和神经元的调节， 苯乙醇胺N-甲基转移酶（PNMT）基因表达 发展这些研究检查了产前和产后 调节酶表达的机制。关于发展的部分 犬嗜睡症的神经生物学使用嗜睡症的动物模型， 常染色体隐性遗传疾病折磨年轻的青少年和儿童， 检查胆碱能和α 1肾上腺素能受体的缺陷。的 研究策略利用相关的差异成熟 神经递质系统帮助定位特定的神经化学物质 病变。在发育受调节的 基因，我们正在设计分离和鉴定基因的方法， 在不同的发育时期表达。我们希望能找出 那些调节大脑结构发育的基因 皮层最后，婴儿的分子和连锁遗传学部分 自闭症描述了寻找婴儿自闭症基因标记的工作， 多发病家庭。

This is a competing renewal application for continuing support of our research program in Molecular Neurobiology and Developmental Disorders. The program consists of an administrative and scientific core serving five major investigative areas. Each area has as its central theme the application of molecular neurobiology to an understanding of developmental processes and their regulation. Studies in the Regulation of Serotonin and beta-adrenergic Receptors section examine the regulation of serotonin and beta-adrenergic receptor mRNA and G-protein coupling during development, as well as the regulation of these receptor mRNAs by antidepressants and drugs which alter neurotransmission. The work seeks to understand those factors which initiate and maintain receptor gene expression. The section on Enzyme Regulation focuses on hormonal and neuronal regulation of phenylethanolamine N-methyltransferase (PNMT) gene expression during development. These studies examine differences in prenatal and postnatal mechanisms regulating enzyme expression. The section on Developmental Neurobiology of Canine Narcolepsy uses an animal model of narcolepsy, an autosomal recessive disorder which afflicts young adolescents and children, to examine defects in cholinergic and alpha(1)-adrenergic receptors. The research strategy utilizes the differential maturation of the relevant neurotransmitter systems to help localize the specific neurochemical lesion(s). In the section on Characterization of Developmentally Regulated Genes, we are devising methods of isolating and characterizing genes which are expressed during discrete developmental epochs. We hope to identify those genes which regulate the architectural development of the cerebral cortex. Finally, the section on Molecular and Linkage Genetics of Infantile Autism describes work seeking to find a gene marker for infantile autism in multiple-incidence families.