PROGRAM IN MOLECULAR NEUROBIOLOGY & DEVELOPMENTAL DISORD

这是对ADAMHA研究科学家奖的修改后的申请。它 部分描述了我作为首席调查员和项目主任的工作 关于分子神经生物学和发育的研究计划 精神错乱。该计划由行政和科学核心组成。 服务于五个主要调查领域。每个领域都有自己的中心主题 分子神经生物学在认识精神分裂症中的应用 发育过程及其调控。监管中的若干问题研究 5-羟色胺和β-肾上腺素能受体部分(Roland D.Ciaranello， M.D.，项目总监)研究5-羟色胺和β-β的调节 肾上腺素能受体mRNA和G蛋白在发育过程中的偶联 抗抑郁药和药物对这些受体mRNAs的调节 这会改变神经传递。这项工作试图理解这些因素 启动和维持受体基因的表达。关于酶的部分 法规(Dona L.Wong博士，项目总监)重点关注荷尔蒙和 苯乙醇胺N-甲基转移酶基因的神经元调控 在发育过程中的表达。这些研究考察了 产前和产后酶表达的调控机制。该节 犬发作性睡病的发育神经生物学(William C.Dement， 医学博士，博士，项目主任)使用了发作性睡病的动物模型，以及 常染色体隐性遗传病，困扰青少年和儿童， 检查胆碱能和α-1-肾上腺素能受体的缺陷。这个 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(S)。在关于发育调节的特征的部分 基因(John L.R.Rubenstein，M.D.，Ph.D.和Roland D.Ciaranello，M.D.， 项目联合董事)，我们正在设计隔离和 描述在离散发育过程中表达的基因 划时代。我们希望找出那些调控建筑的基因 大脑皮层的发育。最后，关于分子和 婴儿自闭症的连锁遗传学(项目F，Luigi Cavalli-Sforza， M.D.，项目主任)描述了为寻找基因标记而进行的工作 多发病家庭中的婴儿自闭症。这位研究科学家 获奖申请在受体部分详细描述了我的工作 调节和自闭症遗传学。

This is a revised application for an ADAMHA Research Scientist Award. It describes in part my work as principal investigator and program director for the 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 (Roland D. Ciaranello, M.D., Project Director) 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 (Dona L. Wong, Ph.D., Project Director) 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 (William C. Dement, M.D., Ph.D., Project Director) 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 (John L.R. Rubenstein, M.D., Ph.D., and Roland D. Ciaranello, M.D, Project Codirectors), we are devising methods of isolating and characterizing genes which are expressed during discrete developmental epoches. 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 (Project F, Luigi Cavalli-Sforza, M.D., Project Director) describes work seeking to find a gene marker for infantile autism in multiple-incidence families. This Research Scientist Award application describes in detail my work in the sections on receptor regulation and autism genetics.