Identifying Neural Substrates of Behavior in Drosophila

这项研究计划的目标是开发并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。利用黑腹果蝇Gal4-UAS基因靶向系统驱动其产物增强或抑制神经元兴奋性的基因表达，我们选择性地上调或下调神经元亚群的活性，并分析这些操作对行为的影响。我们特别感兴趣的是成虫从蛹中羽化后不久所执行的一系列激素协调和发育程序行为，重点是那些翅膀扩张所必需的行为。为了确定这些行为的神经元底物，我们使用了两种方法：一种是定义神经元子集，另一种是随机子集被抑制（分别使用具有定义启动子的Gal4系和Gal4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的模式被确定为进一步的表征。使用第一种方法，我们发现抑制一小部分神经元的电活动，这些神经元表达神经调节剂5 -羟色胺，CCAP（甲壳类心脏活性肽）和滑囊抑制了苍蝇的翅膀扩张。使用第二种方法，我们已经确定了23种抑制模式（即增强-陷阱线），这些模式会产生机翼扩张缺陷。通过使用在重叠的细胞亚群中抑制Gal4转录活性的蝇系进一步限制这些模式（使用Gal80），我们计划鉴定和表征产生这些缺陷的细胞。我们对翅膀扩张行为背后的神经元基质的研究，应该作为一个概念证明？电路映射的方法，以后可以扩展到哺乳动物行为的研究。

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.