Genetics & Circuits/ Innate Avoidance Behavior in Flies

我想研究先天行为是如何受基因控制的。许多对行为至关重要的基因已经被克隆和鉴定。这些行为基因对特定的神经元底物产生影响，反过来又介导行为的表现。我最近与西摩·本泽实验室合作，开发了一种新的果蝇先天回避反应行为测定法--我们称之为“苍蝇恐惧”测定法。在该测定中，果蝇避开T-迷宫中的管，其中一组果蝇先前受到创伤。我假设苍蝇受到创伤发出“报警”的物质，这是认识和避免响应苍蝇。用这个方法，我将从基因上筛选出两组突变体，一组不能释放这种物质，另一组不能避开这种物质。为了给从屏幕上分离的基因提供神经解剖学基础，我将在果蝇大脑中识别出两组基因座，这两组基因座是物质的排放和物质的回避所必需的。 为此，我将使用Gal 4/UAS系统和Shibire的温度敏感等位基因进行无偏电路筛选。一旦基因和回路被识别，我将通过在回路筛选中识别的回路中表达从遗传筛选中识别的基因来挽救行为缺陷。这将统一我们在两个层面上的理解， 基因和电路。

I would like to study how innate behavior is controlled by genes. A number of genes essential for behaviors have been cloned and characterized. These behavior genes exert their influences on specific neuronal substrates which, in turn, mediate the manifestations of the behavior. I recently developed a novel behavior assay for an innate avoidance response in Drosophila in collaboration with Seymour Benzer laboratory- we call it "fly fear" assay. In this assay, fruit flies avoid a tube in a T-maze in which a set of flies were previously traumatized. I hypothesize that flies being traumatized emit "alarm" substance which is recognized and avoided by responder flies. Using this assay, I will genetically screen for two sets of mutants, one failing to emit the substance and another failing to avoid the substance. To provide neuroanatomical basis for genes isolated from the screen, I will identify two sets of loci in the fly brain required for emission of the substance and avoidance of the substance. To do this, I will perform an unbiased circuit screen using the Gal4/UAS system and the temperature sensitive allele of Shibire. Once the genes and circuits are identified, I will rescue the behavior defect by expressing the genes identified from the genetic screen in the circuits identified from the circuit screen. This will unify our understanding at both the level of the gene and of the circuit.