A GAL4-Driver Line Resource for Drosophila Neurobiology.

Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.
Cell Reports (Impact Factor: 7.21). 10/2012; DOI: 10.1016/j.celrep.2012.09.011
Source: PubMed

ABSTRACT We established a collection of 7,000 transgenic lines of Drosophila melanogaster. Expression of GAL4 in each line is controlled by a different, defined fragment of genomic DNA that serves as a transcriptional enhancer. We used confocal microscopy of dissected nervous systems to determine the expression patterns driven by each fragment in the adult brain and ventral nerve cord. We present image data on 6,650 lines. Using both manual and machine-assisted annotation, we describe the expression patterns in the most useful lines. We illustrate the utility of these data for identifying novel neuronal cell types, revealing brain asymmetry, and describing the nature and extent of neuronal shape stereotypy. The GAL4 lines allow expression of exogenous genes in distinct, small subsets of the adult nervous system. The set of DNA fragments, each driving a documented expression pattern, will facilitate the generation of additional constructs for manipulating neuronal function.

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    • "This system allows in vivo repurposing of gene expression patterns through genetic crossing schemes to switch between binary systems (Gal4, LexA, Q) or to achieve intersection by introducing Gal80 or Split-Gal4 hemi-drivers (Gohl et al. 2011) the minimal number of cells required for a behavior may be inhibited by the lack of enhancer-trap expression patterns with sufficiently restricted patterns to be informative for mapping. It may require the combination of a collection of enhancer-trap or promoter-driven Gal4 lines and ET-FLP lines to produce smaller intersection patterns (Pfeiffer et al. 2008; Jenett et al. 2012). Third, the number of ET-FLPx2 lines currently available most likely limits the power of the FINGR system. "
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    ABSTRACT: Understanding behavior requires unraveling the mysteries of neurons, glia, and their extensive connectivity. Drosophila has emerged as an excellent organism for studying the neural basis of behavior. This can be largely attributed to the extensive effort of the fly community to develop numerous sophisticated genetic tools for visualizing, mapping, and manipulating behavioral circuits. Here, we attempt to highlight some of the new reagents, techniques and approaches available for dissecting behavioral circuits in Drosophila. We focus on detailing intersectional strategies such as the Flippase-induced intersectional Gal80/Gal4 repression (FINGR), because of the tremendous potential they possess for mapping the minimal number of cells required for a particular behavior. The logic and strategies outlined in this review should have broad applications for other genetic model organisms.
    Journal of Comparative Physiology 04/2015; DOI:10.1007/s00359-015-1010-y · 1.63 Impact Factor
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    • "The presynaptic terminals from 0104-labeled dopaminergic neurons densely innervate the b 0 and g lobe tips of the horizontal mushroom body lobes, which suggests that appetitive olfactory memories may be represented as changes in the efficacy of synaptic outputs in these regions from the odor-activated KCs onto as-yet-unidentified downstream neurons. By visually screening available GAL4 collections (Jenett et al., 2012; Bidaye et al., 2014), we identified three fly lines that labeled candidate postsynaptic neurons with arbors in the tip regions, b 2 , b 0 2 , and g 5 , of the horizontal mushroom body lobes (Figure 1). Neurons innervating b 0 2 and g 5 have been described as MB-M4 and MB-M6 (Tanaka et al., 2008). "
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    ABSTRACT: During olfactory learning in fruit flies, dopaminergic neurons assign value to odor representations in the mushroom body Kenyon cells. Here we identify a class of downstream glutamatergic mushroom body output neurons (MBONs) called M4/6, or MBON-β2β'2a, MBON-β'2mp, and MBON-γ5β'2a, whose dendritic fields overlap with dopaminergic neuron projections in the tips of the β, β', and γ lobes. This anatomy and their odor tuning suggests that M4/6 neurons pool odor-driven Kenyon cell synaptic outputs. Like that of mushroom body neurons, M4/6 output is required for expression of appetitive and aversive memory performance. Moreover, appetitive and aversive olfactory conditioning bidirectionally alters the relative odor-drive of M4β' neurons (MBON-β'2mp). Direct block of M4/6 neurons in naive flies mimics appetitive conditioning, being sufficient to convert odor-driven avoidance into approach, while optogenetically activating these neurons induces avoidance behavior. We therefore propose that drive to the M4/6 neurons reflects odor-directed behavioral choice. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Neuron 04/2015; DOI:10.1016/j.neuron.2015.03.025 · 15.98 Impact Factor
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    • "DEVELOPMENT classes. The vast catalog of new transgenic drivers in the FlyLight Gal4 library (Jenett et al., 2012) provides an unrivaled opportunity for targeted control of individually identifiable neurons. Activitydependent restructuring underlying refinement of synaptic partnerships could be further pursued in conjunction with new mapping strategies, such as genetic reconstitution across synaptic partners (GRASP) (Feinberg et al., 2008) or the CaLexA system of neural tracing (Masuyama et al., 2012). "
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    ABSTRACT: The activity-dependent refinement of neural circuit connectivity during critical periods of brain development is essential for optimized behavioral performance. We hypothesize that this mechanism is defective in fragile X syndrome (FXS), the leading heritable cause of intellectual disability and autism spectrum disorders. Here, we use optogenetic tools in the Drosophila FXS disease model to test activity-dependent dendritogenesis in two extrinsic neurons of the mushroom body (MB) learning and memory brain center: (1) the input projection neuron (PN) innervating Kenyon cells (KCs) in the MB calyx microglomeruli and (2) the output MVP2 neuron innervated by KCs in the MB peduncle. Both input and output neuron classes exhibit distinctive activity-dependent critical period dendritic remodeling. MVP2 arbors expand in Drosophila mutants null for fragile X mental retardation 1 (dfmr1), as well as following channelrhodopsin-driven depolarization during critical period development, but are reduced by halorhodopsin-driven hyperpolarization. Optogenetic manipulation of PNs causes the opposite outcome - reduced dendritic arbors following channelrhodopsin depolarization and expanded arbors following halorhodopsin hyperpolarization during development. Importantly, activity-dependent dendritogenesis in both neuron classes absolutely requires dfmr1 during one developmental window. These results show that dfmr1 acts in a neuron type-specific activity-dependent manner for sculpting dendritic arbors during early-use, critical period development of learning and memory circuitry in the Drosophila brain. © 2015. Published by The Company of Biologists Ltd.
    Development 04/2015; 142(7):1346-56. DOI:10.1242/dev.117127 · 6.27 Impact Factor