Identifying Neural Substrates of Behavior in Drosophila

识别果蝇行为的神经基础

• 批准号: 6982718
• 负责人: Benjamin H White
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6982718
• 关键词: Drosophilidae; animal genetic material tag; behavioral /social science research tag; behavioral genetics; brain electrical activity; brain mapping; cell line; ethology; gene expression; gene targeting; hormone regulation /control mechanism; limb movement; metamorphosis; neural inhibition; neural transmission; neurohormones; neurons; neuropeptides; neuropsychology; neuroregulation; serotonin; technology /technique development

The goal of this research program is to exploit, and further develop, techniques for manipulating neural activity to identify the brain circuits underlying specific behaviors. Using the Gal4-UAS gene targeting system of Drosophila melanogaster to drive the expression of genes whose products enhance or inhibit neuronal excitability, we are selectively up- or down-regulating the activity of subsets of neurons and analyzing the effects of these manipulations on behavior. We are particularly interested in the suite of hormonally coordinated and developmentally programmed behaviors executed by the adult fly shortly after emergence from the pupal case, with a focus on those necessary for wing expansion. To identify neuronal substrates of these behaviors we use two approaches: one in which defined subsets of neurons, and the other in which random subsets, are inhibited (using Gal4 lines with defined promoters and Gal4 enhancer-trap lines, respectively). In each case, patterns of suppression or enhancement that affect the behaviors of interest are identified for further characterization. Using the first approach, we have found that inhibition of electrical activity in a small subset of neurons that express the neuromodulators serotonin, CCAP (crustacean cardioactive peptide) and bursicon suppresses wing expansion in flies. Using the second approach, we have identified 23 patterns of suppression (i.e. enhancer-trap lines) that generate wing expansion deficits. By further restricting these patterns using fly lines that inhibit Gal4 transcriptional activity in overlapping subsets of cells (using Gal80) we plan to identify and characterize the cells responsible for generating these deficits. Our investigation of the neuronal substrates underlying wing expansion behavior should serve as a ?proof of concept? of a circuit mapping approach that can later be extended to studies of mammalian behavior.

这项研究计划的目标是利用和进一步发展操纵神经活动的技术，以识别特定行为背后的大脑回路。使用果蝇的Gal 4-UAS基因靶向系统来驱动其产物增强或抑制神经元兴奋性的基因的表达，我们选择性地上调或下调神经元子集的活性，并分析这些操作对行为的影响。我们特别感兴趣的是一套由成年苍蝇从蛹的情况下出现后不久执行的协调和发育程序化的行为，重点是那些必要的翅膀扩张。为了识别这些行为的神经元底物，我们使用两种方法：一种是定义的神经元子集，另一种是随机子集，被抑制（分别使用具有定义的启动子的Gal 4系和Gal 4增强子-陷阱系）。在每种情况下，影响感兴趣的行为的抑制或增强模式被识别用于进一步表征。使用第一种方法，我们已经发现，在一小部分表达神经调节剂5-羟色胺，CCAP（甲壳动物心脏活性肽）和bursicon的神经元中抑制电活动会抑制苍蝇的翅膀扩张。使用第二种方法，我们已经确定了23种模式的抑制（即增强陷阱线），产生机翼扩张赤字。通过使用在重叠的细胞亚群中抑制Gal 4转录活性的飞线（使用Gal 80）进一步限制这些模式，我们计划鉴定和表征负责产生这些缺陷的细胞。我们的调查背后的翅膀扩张行为的神经基板应作为一个？概念验证？这是一种电路映射方法，以后可以扩展到哺乳动物行为的研究。