Neuroadaptations to Ethanol in Drosophila

果蝇对乙醇的神经适应

基本信息

批准号：
7291100
负责人：
Therese A Kosten
金额：
$ 22.17万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-09-27 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7291100
关键词：
Adult Affinity Alcoholism Architecture Area Attention Behavior Behavioral Binding Proteins Biochemical Biological Biological Assay Boutos Brain Chromosome Pairing Chronic Collaborations Complex Data Development Doctor of Philosophy Dominant-Negative Mutation Drosophila genus Epitopes Ethanol Exhibits Exposure to Gene Expression Gene Expression Regulation Genes Genetic Goals Head Hour Hypersensitivity Indiana Learning Maps Mediating Memory Messenger RNA Modeling Molecular Molecular Genetics Molecular Profiling Mus Mutant Strains Mice Names Neurons Neurotransmitter Receptor Pattern Phenotype Physiological Predisposition Protein Biosynthesis Proteins RNA RNA Interference RNA-Binding Proteins Research Research Personnel Research Project Grants Scaffolding Protein Series Signal Pathway Suggestion Synapses Techniques Testing Time Transgenes Universities alcohol behavior alcohol effect alcohol exposure alcohol response alcohol sensitivity base day experience fly gene function insight medical schools mutant neuroadaptation postsynaptic protein function research study response sedative trafficking transgene expression vapor

项目摘要

DESCRIPTION (provided by applicant): The long-term goals of this research project are to elucidate the molecular and cellular mechanisms for neuroadaptations to ethanol. Previous studies have identified two new Drosophila mutants with a heightened sensitivity and impaired tolerance to ethanol. Preliminary spatial expression studies of one mutant, named homer, have suggested that the normal gene's function is sufficient in GABAergic neurons that innervate the ellipsoid body for normal behavioral responses to ethanol. These studies will be confirmed and extended. In addition, the directed expression of RNAi constructs and dominant negatives will be used to define where Corner expression is required in the adult brain for wild type behavioral responses to ethanol. Newly developed techniques that provide for experimenter control over transgene expression in time and space will be used to ascertain whether homer is required during development or whether it is required physiologically in the adult fly. Similar time and space expression studies using a normal transgene of the second mutant, named yps, will be performed to ascertain whether this gene's function is required in the same set of neurons and at the same time as homer for normal ethanol responses. RNA from neurons that require homer and/or yps will be isolated using newly developed affinity techniques and used to probe microarrays to define the changes in gene expression that occur with ethanol exposure in this specific set of neurons. The observed changes in gene expression with ethanol exposure will be used to predict which genes are functionally involved in behavioral responses to ethanol, and mutants in these genes will be assayed to further define the molecular genetic requirements for normal ethanol sensitivity and tolerance. These studies will further our understanding of the genetic basis for ethanol sensitivity and tolerance, important parameters for susceptibility to alcoholism.

描述（由申请人提供）：该研究项目的长期目标是阐明针对乙醇神经适应的分子和细胞机制。先前的研究已经确定了两个新的果蝇突变体，其灵敏度增强和对乙醇的耐受性受损。一个名为Homer的一个突变体的初步空间表达研究表明，正常基因的功能足以使椭圆形体内的GABA能神经元对正常的行为反应对乙醇产生。这些研究将得到确认并扩展。此外，RNAi构建体的定向表达和主要的负面因素将用于定义成年大脑中需要角度表达的野生型行为对乙醇的反应。新开发的技术可以使用时间和空间中对转基因表达的实验者控制，以确定在开发过程中是否需要荷马或在成年蝇中需要生理上需要的荷马。使用第二个突变体的正常转基因（称为YPS）进行类似的时间和空间表达研究，以确定在同一神经元中是否需要该基因的功能，并且与荷马同时需要正常的乙醇反应。来自需要本垒打和/或YP的神经元的RNA将使用新开发的亲和力技术分离，并用于探测微阵列以定义这一特定神经元中乙醇暴露的基因表达变化。观察到的与乙醇暴露的基因表达变化将用于预测哪些基因在功能上与行为反应有关，并且将分析这些基因中的突变体以进一步定义正常乙醇敏感性和耐受性的分子遗传需求。这些研究将进一步理解乙醇敏感性和耐受性的遗传基础，这是对酒精中毒易感性的重要参数。