http://precedings.nature.com/tags/Drosophila Recently posted documents tagged with 'Drosophila' Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://dx.doi.org/10.1038/npre.2009.3980.1 Drosophila neuro-anatomical data is scattered across a large, diverse literature dating back over 75 years and a growing number of community databases. Lack of a standardized nomenclature for neuro-anatomy makes comparison and searching this growing data-set extremely arduous. A recent standardization effort (BrainName; Manuscript in preparation) has produced a segmented, 3D model of the Drosophila brain annotated with a controlled vocabulary. We are formalizing these developments to produce a web-based ontology-linked atlas in which gross brain anatomy is defined, in part, by labeled volumes in a standard reference brain.We have developed new relations that allow us to use this well-defined gross anatomy as a substrate to define neuronal types according to where they fasciculate and innervate as well as to record the neurotransmitters they release, their lineage and functions. The resulting ontology will provide a vocabulary for annotation and a means for integrative queries of neurobiological data.The ontology and associated images, queries and annotations will be integrated into the Virtual Fly Brain website. This will provide a resource that biologists can use to browse annotated images of Drosophila neuro-anatomy and to get answers to questions about that anatomy and related data, without any need for ontology expertise. http://dx.doi.org/10.1038/npre.2009.3980.1 Tue, 17 Nov 2009 11:24:20 UTC Virtual Fly Brain: An ontology-linked schema of the Drosophila Brain doi:10.1038/npre.2009.3980.1 2009-11-17 David J. Osumi-Sutherland Nature Precedings 2009-11-17T11:24:20Z Poster Neuroscience Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3460/version/1 A male Drosophila model of locomotor deficit induced by chronic pentylenetetrazole (PTZ), a proconvulsant used to model epileptogenesis in rodents, has recently been described. Antiepileptic drugs (AEDs) ameliorate development of this behavioral abnormality. Time-series of microarray profiling of heads of male flies treated with PTZ has shown epileptogenesis-like transcriptomic perturbation in the fly model. Gender differences are known to exist in neurological and psychiatric conditions including epileptogenesis. We describe here the effects of chronic PTZ in Drosophila females, and compare the results with the male model. As in males, chronic PTZ was found found to cause a decreased climbing speed in females. In males, overrepresentation of Wnt, MAPK, TGF-beta, JAK-STAT, Cell communication, and Dorso-Ventral axis formation pathways in downregulated genes was previously described. Of these, female genes showed enrichment only for Dorso-Ventral axis formation. Most significant, ribosomal pathway was uniquely overrepresented in genes downregulated in females. Gender differences thus exist in the Drosophila model. Gender neutral, Dorso-Ventral axis formation may be considered as the candidate causal pathway in chronic pentylenetetrazole induced behavioral deficit. Prior evidence of developmental mechanisms in epileptogenesis underscores the usefulness of fly model. Gender specific pathways may provide a lead for understanding brain dimorphism in neuropsychiatric disorders. http://precedings.nature.com/documents/3460/version/1 Mon, 27 Jul 2009 20:02:00 UTC Gender differences in a Drosophila transcriptomic model of chronic pentylenetetrazole induced behavioral deficit hdl:10101/npre.2009.3460.1 2009-07-27 Abhay Sharma Nature Precedings 2009-07-27T20:02:00Z Manuscript Genetics & Genomics Neuroscience Pharmacology Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3447/version/1 Rodent kindling induced by pentylenetetrazole (PTZ) is an established model of epileptogenesis and antiepileptic drug (AED) testing. Recently, a Drosophila systems model has been described in which chronic PTZ causes a decreased climbing speed in adult males on 7th day. Some AEDs ameliorate development of this locomotor deficit. Time-series of microarray expression profiles of heads of flies treated with PTZ has been found to resemble transcriptomic alterations associated with epileptogenesis. In the fly model, withdrawal from seven day long PTZ treatment causes an increased climbing speed on 7th consequent day. Here, we present a systems model of the post-PTZ withdrawal regime. Unlike AED-untreated individuals, flies treated with any of the five AEDs after PTZ discontinuation exhibited normal climbing speed on 7th day, i.e., 14th day from the beginning of PTZ treatment. Time-series of microarray expression profiles of fly heads comparing control PTZ- and AED-untreated, and AED-untreated post PTZ withdrawal groups showed differentially expressed genes throughout. These genes enriched gene ontology (GO) molecular functions including transcription regulator and GTPase regulator activities. Interestingly, expression profiles of fly heads comparing control PTZ- and AED-untreated, and AED-treated post PTZ withdrawal groups showed neutralization of transcription regulator and GTPase regulator activities by the AEDs. Further transcriptomic analysis based on overinteraction in protein interactome and enrichment of miRNA targets implicated axon guidance and neuronal remodeling related perturbations in the fly model. Differential expression of genes belonging to transcription regulator and GTPase regulator activities have previously been reported in post-epileptogenesis in established rodent models. Also, axon guidance and neuronal remodeling related alterations have been implicated in epilepsy. The Drosophila model thus provides a unique opportunity to dissect long-term plasticity relevant in epileptogenesis at cellular and molecular levels. Besides, the model also offers an excellent system to efficiently screen agents with potential therapeutic activity. http://precedings.nature.com/documents/3447/version/1 Tue, 21 Jul 2009 16:40:03 UTC A Drosophila systems model of withdrawal from chronic pentylenetetrazole relevant in post-epileptogenesis hdl:10101/npre.2009.3447.1 2009-07-21 Abhay Sharma Nature Precedings 2009-07-21T16:40:03Z Manuscript Genetics & Genomics Neuroscience Pharmacology Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3429/version/1 In a newly described Drosophila model, two of the five antiepileptic drugs (AEDs) tested, sodium valproate (NaVP) and levetiracetam (LEV), not ethosuximide (ETH), gabapentin (GBP) and vigabatrin (VGB), ameliorate development of chronic pentylenetetrazole (PTZ) induced locomotor alteration. To further characterize the model, we analyze here the microarray expression profile of heads of flies treated with depolarizing compound potassium chloride (KCl). Surprisingly, microarray clustering showed unexpected similarity among KCl, LEV and NaVP. Further, like the two effective AEDs in the fly model, KCl regulated genes overrepresented ribosomal pathway. Interestingly, KCl also ameliorated development of locomotor deficit in the chronic PTZ model. Both transcriptomic and behavioral analyses thus showed LEV- and NaVP- like neuroprotective effect of KCl. This is consistent with neuroprotective effect of KCl observed previously in mammalian system. The Drosophila model thus provides a unique opportunity to understand long term mechanisms of neuroactive compounds. http://precedings.nature.com/documents/3429/version/1 Fri, 17 Jul 2009 14:41:20 UTC A novel Drosophila transcriptomic and behavioral model detects potassium chloride with therapeutic potential hdl:10101/npre.2009.3429.1 2009-07-17 Abhay Sharma Nature Precedings 2009-07-17T14:41:20Z Manuscript Genetics & Genomics Neuroscience Pharmacology Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3418/version/1 A Drosophila behavioral and transcriptomic model of locomotor plasticity induced by chronic pentylenetetrazole (PTZ) has recently been developed. In this model, two of the five antiepileptic drugs (AEDs) tested, sodium valproate (NaVP) and levetiracetam (LEV), not ethosuximide (ETH), gabapentin (GBP) and vigabatrin (VGB), ameliorate development of chronic PTZ induced locomotor alteration. Transcriptomic effect of the AEDs and PTZ in fly head has been described. Here, we analyze microarray expression profile of heads of flies treated with the convulsants tetraethylammonium chloride (TEA) and pilocarpine hydrochloride (PILO). Strikingly, microarray clustering placed TEA, not PILO, with LEV and NaVP in one group that was distinct from the other one consisting of PTZ, GBP, VGB and ETH. Further, like LEV and NaVP, TEA regulated genes overrepresented ribosomal and energy metabolic pathways. Also, TEA, like LEV and NaVP, ameliorated development of locomotor deficit in the chronic PTZ model. Both transcriptomic and behavioral analyses thus demonstrated LEV- and NaVP- like neuroprotective effect of TEA. Our results are consistent with earlier paradoxical evidence suggesting that TEA may be neuroprotective. Amenability of Drosophila model thus provides an excellent opportunity to understand long term mechanisms of action of centrally acting drugs in molecular details. http://precedings.nature.com/documents/3418/version/1 Fri, 10 Jul 2009 14:58:20 UTC A novel Drosophila post-genomic CNS drug discovery model detects tetraethylammonium chloride with therapeutic potential hdl:10101/npre.2009.3418.1 2009-07-10 Abhay Sharma Nature Precedings 2009-07-10T14:58:20Z Manuscript Genetics & Genomics Neuroscience Pharmacology Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3396/version/1 Mechanisms of long term action of antiepileptic drugs (AEDs), used in treating epilepsy and many other neurological and psychiatric disorders, are poorly understood. Recently, a novel Drosophila transcriptomic model of locomotor plasticity induced by chronic pentylenetetrazole (PTZ), a chemoconvulsant commonly used to model epileptogenesis and test AEDs in rodents, has been described. In this model, two of the five AEDs tested, sodium valproate (NaVP) and levetiracetam (LEV), not ethosuximide (ETH), gabapentin (GBP) and vigabatrin (VGB), ameliorate development of chronic PTZ induced locomotor alteration. Here, we describe transcriptomic effect of the AEDs in the fly model. Singular treatment with ETH, GBP and VGB in general caused downregulation of genes. In contrast, similar treatment with NaVP and LEV caused upregulation. The GBP and NaVP gene sets showed enrichment of the ribosomal and energy metabolic pathways. The network partners of ETH, VGB and LEV regulated genes in the available interactome map were also found to overrepresent the ribosomal pathway. Unlike PTZ alone, PTZ and LEV combination treatment was found to cause differential regulation of genes that too enriched the ribosomal and energy metabolic pathways. Cumulatively, we provide transcriptomic evidence that suggests involvement of ribosomal and energy metabolic mechanisms in AED action. The Drosophila model provides an excellent opportunity to further understand mechanisms of AED action in molecular details. http://precedings.nature.com/documents/3396/version/1 Tue, 07 Jul 2009 16:27:35 UTC Transcriptomic analysis implicates ribosomal and energy metabolic pathways in antiepileptic drug action in a Drosophila model hdl:10101/npre.2009.3396.1 2009-07-07 Abhay Sharma Nature Precedings 2009-07-07T16:27:35Z Manuscript Genetics & Genomics Neuroscience Pharmacology Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3402/version/1 We propose a new model describing the production and the establishment of the stable gradient of the Bicoid protein along the antero-posterior axis of the embryo of Drosophila. In this model, we consider that bicoid mRNA diffuses along the antero-posterior axis of the embryo and the protein is produced in the ribosomes localized near the syncytial nuclei. Bicoid protein stays localized near the syncytial nuclei as observed in experiments.We calibrate the parameters of the mathematical model with experimental data taken during the cleavage stages 11 to 14 of the developing embryo of Drosophila. We obtain good agreement between the experimental and the model gradients, with relative errors in the range 5-8%. The inferred diffusion coefficient of bicoid mRNA is in the range 4.6×10-12 – 1.5×10-11 m2s-1, in agreement with the theoretical predictions and experimental measurements for the diffusion of macromolecules in the cytoplasm. We show that the model based on the mRNA diffusion hypothesis is consistent with the known observational data, supporting the recent experimental findings of the gradient of bicoid mRNA in Drosophila [Spirov et al. (2009) Development 136:605-614]. http://precedings.nature.com/documents/3402/version/1 Mon, 06 Jul 2009 15:07:15 UTC mRNA diffusion explains protein gradients in Drosophila early development hdl:10101/npre.2009.3402.1 2009-07-06 Rui Dilao Nature Precedings 2009-07-06T15:07:15Z Manuscript Developmental Biology Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2009.2926.1 Learning about the consequences of our actions (operant learning) is one of the major ways in which we learn to understand the world we live in. Despite our recent advances in the neurobiology of learning and memory, this “learning-by-doing” has largely withstood neurobiological scrutiny. This proposal aims to elucidate the molecular and neurobiological mechanisms of spontaneous behavioral choice and how decision-making is modulated by the consequences of such actions. This research will be done in a genetically amenable model system, the fruit fly Drosophila. We will use state-of-the-art genetic and behavioral techniques to identify the circuitry and molecular processes involved in generating spontaneous turning behavior and its modulation by operant learning. Operant learning is only one system among many which govern the organization of behavior. The long-term prospect of this research beyond this application is to understand how multiple memory systems interact to accomplish adaptive behavioral choice and decision-making. http://dx.doi.org/10.1038/npre.2009.2926.1 Fri, 06 Mar 2009 17:24:26 UTC The neurobiology of spontaneous actions and operant learning in Drosophila doi:10.1038/npre.2009.2926.1 2009-03-06 Björn Brembs Nature Precedings 2009-03-06T17:24:26Z Presentation Neuroscience http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2008.2171.1 Our past experience is one of the primary sources of information when faced with a choice. We ask ourselves: “what will happen if I do this?” Accurately predicting the consequences of our actions is usually modeled by operant (instrumental) learning experiments. These types of experiments are often contrasted with classical (Pavlovian) conditioning experiments in a dichotomy. And indeed, different brain circuits mediate the acquisition of skills and habits (via operant/instrumental learning) and the acquisition of facts (via classical/Pavlovian learning). However, realistic learning situations always comprise interactions of skill- and fact-learning components (composite learning). Fixed flying Drosophila melanogaster at the torque meter provide one of the very few systems where the relationship of operant and classical predictors in composite learning can be studied with sufficient rigor. The latest experiments show that the textbook operant/classical dichotomy is misleading and that instead composite learning consists of multiple interacting memory systems. These interactions between predictive stimuli (classical component) and goal-directed actions (operant component) make composite conditioning more effective than the operant and classical components alone (learning-by-doing, generation effect). Rutabaga (rut) mutants are impaired in learning about the (classical) stimuli, but show improved (operant) behavior learning. This is the first evidence that operant and classical conditioning differ not only at the circuit, but also at the molecular level. The interaction between operant and classical components is reciprocal and hierarchical, such that the classical suppresses the operant component. Experiments with transgenic flies demonstrate that this suppression of operant learning is mediated by the mushroom-bodies and serves to ensure that the classical memories can be generalized for access by other behaviors. Extended training can overcome this suppression and transforms goal-directed actions into habitual responses. This interaction leads to efficient learning, enables generalization and prevents premature habit-formation. http://dx.doi.org/10.1038/npre.2008.2171.1 Wed, 17 Sep 2008 12:49:48 UTC Mushroom-bodies regulate habit formation in Drosophila doi:10.1038/npre.2008.2171.1 2008-09-17 Björn Brembs Nature Precedings 2008-09-17T12:49:48Z Presentation Genetics & Genomics Neuroscience http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/1831/version/1 Recent geological models indicate a marked increase in atmospheric oxygen partial pressure (aPO2) to 32 kPa in the Permo-Carboniferous (approx. 300 million years ago), subsequently falling to 13 kPa in the Triassic1.These aPO2 changes have been hypothesized to cause multiple major evolutionary events2 including the appearance and subsequent extinction of giant insects and other taxa3, 4. Patterns of increasing tracheal investment in larger insects support this hypothesis5, as do observations of positive relationships between aPO2 and body size in single- or multi-generational experiments with Drosophila melanogaster and other insects6. Large species likely result from many generations of selection for large body size driven by predation, competition or sexual selection7. Thus a crucial question is whether aPO2 influences the capacity of such selection to increase insect size. We tested that possibility by selecting for large body size in five Drosophila melanogaster populations for 11 generations in hypoxic (10 kPa), normoxic (21 kPa) and hyperoxic (40 kPa) aPO2, followed by three generations of normoxia without size selection to test for evolved responses. Average body sizes increased by 15% during 11 generations of size selection in 21 and 40 kPa aPO2 flies and even stronger responses were observed for the flies in the largest quartile of body masses. However, flies selected for large size in 10 kPa aPO2 had strongly reduced sizes compared to those in higher aPO2. Upon return to normoxia, all flies had similar, enlarged sizes relative to the starting populations. These results demonstrated that positive size selection had equivalent genetic effects on all flies independent of aPO2, but that hypoxia provided a physical constraint on body size even in a relatively small insect under strong selection for larger mass. Our data support the hypothesis that Triassic hypoxia may have contributed to a reduction in insect size. http://precedings.nature.com/documents/1831/version/1 Fri, 25 Apr 2008 14:16:09 UTC Atmospheric hypoxia limits selection for large body size in insects hdl:10101/npre.2008.1831.1 2008-04-25 C Jaco Klok Nature Precedings 2008-04-25T14:16:09Z Manuscript Ecology Evolutionary Biology http://creativecommons.org/licenses/by/3.0/