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ABSTRACT: In a wide range of animals, uncontrollable stressful events can induce a condition called "learned helplessness." In mammals it is associated with low general activity, poor learning, disorders of sleep and feeding, ulcers, and reduced immune status, as well as with increased serotonin in parts of the brain. It is considered an animal model of depression in humans [1-4]. Here we investigate learned helplessness in Drosophila, showing that this behavioral state consists of a cognitive and a modulatory, possibly mood-like, component. A fly, getting heated as soon as it stops walking, reliably resumes walking to escape the heat. If, in contrast, the fly is not in control of the heat, it learns that its behavior has no effect and quits responding. In this state, the fly walks slowly and takes longer and more frequent rests, as if it were "depressed." This downregulation of walking behavior is more pronounced in females than in males. Learned helplessness in Drosophila is an example of how, in a certain situation, behavior is organized according to its expected consequences.
Current biology: CB 04/2013; · 10.99 Impact Factor
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ABSTRACT: Visual behavior of insects has long been studied, but it is only recently that a wide variety of genetic tools has become available for its analysis. Perhaps the most basic visual behaviour is phototaxis, locomotion towards a source of light. It is known in many insects and has been studied for over a century but the neural network underlying it is little understood. We recently described in the fruit fly Drosophila how different photoreceptor types contribute to phototaxis. By blocking subsets of them we showed that at least four of the five types are involved. In this short review, we compare phototactic behaviour in fruit flies and other insects (especially honeybees), and discuss what is known about the underlying neural circuitry. :
Fly 10/2011; 5(4). · 1.30 Impact Factor
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ABSTRACT: Organisms with complex visual systems rarely respond to just the sum of all visual stimuli impinging on their eyes. Often, they restrict their responses to stimuli in a temporarily selected region of the visual field (selective visual attention). Here, we investigate visual attention in the fly Drosophila during tethered flight at a torque meter. Flies can actively shift their attention; however, their attention can be guided to a certain location by external cues. Using visual cues, we can direct the attention of the fly to one or the other of the two visual half-fields. The cue can precede the test stimulus by several seconds and may also be spatially separated from the test by at least 20° and yet attract attention. This kind of external guidance of attention is found only in the lower visual field.
Proceedings of the National Academy of Sciences 04/2011; 108(17):7230-5. · 9.68 Impact Factor
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Martin Heisenberg
Journal of neurogenetics 09/2010; 24(3):93-4. · 0.73 Impact Factor
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ABSTRACT: The visual systems of most species contain photoreceptors with distinct spectral sensitivities that allow animals to distinguish lights by their spectral composition. In Drosophila, photoreceptors R1-R6 have the same spectral sensitivity throughout the eye and are responsible for motion detection. In contrast, photoreceptors R7 and R8 exhibit heterogeneity and are important for color vision. We investigated how photoreceptor types contribute to the attractiveness of light by blocking the function of certain subsets and by measuring differential phototaxis between spectrally different lights. In a "UV vs. blue" choice, flies with only R1-R6, as well as flies with only R7/R8 photoreceptors, preferred blue, suggesting a nonadditive interaction between the two major subsystems. Flies defective for UV-sensitive R7 function preferred blue, whereas flies defective for either type of R8 (blue- or green-sensitive) preferred UV. In a "blue vs. green" choice, flies defective for R8 (blue) preferred green, whereas those defective for R8 (green) preferred blue. Involvement of all photoreceptors [R1-R6, R7, R8 (blue), R8 (green)] distinguishes phototaxis from motion detection that is mediated exclusively by R1-R6.
Proceedings of the National Academy of Sciences 03/2010; 107(12):5634-9. · 9.68 Impact Factor
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ABSTRACT: Current imaging methods such as Magnetic Resonance Imaging (MRI), Confocal microscopy, Electron Microscopy (EM) or Selective Plane Illumination Microscopy (SPIM) yield three-dimensional (3D) data sets in need of appropriate computational methods for their analysis. The reconstruction, segmentation and registration are best approached from the 3D representation of the data set.
Here we present a platform-independent framework based on Java and Java 3D for accelerated rendering of biological images. Our framework is seamlessly integrated into ImageJ, a free image processing package with a vast collection of community-developed biological image analysis tools. Our framework enriches the ImageJ software libraries with methods that greatly reduce the complexity of developing image analysis tools in an interactive 3D visualization environment. In particular, we provide high-level access to volume rendering, volume editing, surface extraction, and image annotation. The ability to rely on a library that removes the low-level details enables concentrating software development efforts on the algorithm implementation parts.
Our framework enables biomedical image software development to be built with 3D visualization capabilities with very little effort. We offer the source code and convenient binary packages along with extensive documentation at http://3dviewer.neurofly.de.
BMC Bioinformatics 01/2010; 11:274. · 2.75 Impact Factor
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ABSTRACT: Mutations in Ribosomal s6 kinase 2 (Rsk2) are associated with severe neuronal dysfunction in Coffin-Lowry syndrome (CLS) patients, flies and mice. So far, the mechanisms of how Rsk2 regulates development, maintenance and activity of neurons are not understood. We have investigated the consequences of Rsk2 deficiency in mouse spinal motoneurons. Survival of isolated Rsk2 deficient motoneurons is not reduced, but these cells grow significantly longer neurites. Conversely, overexpression of a constitutively active form of Rsk2 leads to reduced axon growth. Increased axon growth in Rsk2 deficient neurons was accompanied by higher Erk 1/2 phosphorylation, and the knockout phenotype could be rescued by pharmacological inhibition of MAPK/Erk kinase (Mek). These data indicate that Rsk2 negatively regulates axon elongation via the MAPK pathway. Thus, the functional defects observed in the nervous system of CLS patients and animal models with Rsk2 deficiency might be caused by dysregulated neurite growth rather than primary neurodegeneration.
Molecular and Cellular Neuroscience 07/2009; 42(2):134-41. · 3.66 Impact Factor
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Martin Heisenberg
Nature 06/2009; 459(7244):164-5. · 36.28 Impact Factor
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ABSTRACT: Ribosomal S6 kinases (RSKs) are growth factor-regulated serine-threonine kinases participating in the RAS-ERK signaling pathway. RSKs have been implicated in memory formation in mammals and flies. To characterize the function of RSK at the synapse level, we investigated the effect of mutations in the rsk gene on the neuromuscular junction (NMJ) in Drosophila larvae. Immunostaining revealed transgenic expressed RSK in presynaptic regions. In mutants with a full deletion or an N-terminal partial deletion of rsk, an increased bouton number was found. Restoring the wild-type rsk function in the null mutant with a genomic rescue construct reverted the synaptic phenotype, and overexpression of the rsk-cDNA in motoneurons reduced bouton numbers. Based on previous observations that RSK interacts with the Drosophila ERK homologue Rolled, genetic epistasis experiments were performed with loss- and gain-of-function mutations in Rolled. These experiments provided evidence that RSK mediates its negative effect on bouton formation at the Drosophila NMJ by inhibition of ERK signaling.
Developmental Neurobiology 02/2009; 69(4):212-20. · 3.55 Impact Factor
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ABSTRACT: Even in a simple Pavlovian memory task an animal may form several associations that can be independently assessed by the appropriate tests. Studying conditioned odor discrimination of the fruit fly Drosophila melanogaster we found that animals store quality and intensity of an odor as separate memory traces. The trace of odor intensity is short-lived, decaying in <3 h. Only the last intensity value is stored. In contrast to odor-quality memory, odor-intensity memory does not require the rutabaga-dependent cAMP signaling pathway. Flies rely on their memory of intensity in a narrow concentration range in which they can generalize intensity. Larger concentration differences they treat like different qualities. This study shows that the perceptual identity of an odor is based on at least three lines of processing in the brain: (i) a memory of odor quality, (ii) a memory of odor intensity, and (iii) a range of intensities (and qualities), in which the odor is generalized.
Proceedings of the National Academy of Sciences 10/2008; 105(41):15985-90. · 9.68 Impact Factor
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ABSTRACT: Whether motion vision uses color contrast is a controversial issue that has been investigated in several species, from insects to humans. We used Drosophila to answer this question, monitoring the optomotor response to moving color stimuli in WT and genetic variants. In the fly eye, a motion channel (outer photoreceptors R1-R6) and a color channel (inner photoreceptors R7 and R8) have been distinguished. With moving bars of alternating colors and high color contrast, a brightness ratio of the two colors can be found, at which the optomotor response is largely missing (point of equiluminance). Under these conditions, mutant flies lacking functional rhodopsin in R1-R6 cells do not respond at all. Furthermore, genetically eliminating the function of photoreceptors R7 and R8 neither alters the strength of the optomotor response nor shifts the point of equiluminance. We conclude that the color channel (R7/R8) does not contribute to motion detection as monitored by the optomotor response.
Proceedings of the National Academy of Sciences 04/2008; 105(12):4910-5. · 9.68 Impact Factor
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ABSTRACT: In mammals and humans, noradrenaline is a key modulator of aggression. Octopamine, a closely related biogenic amine, has been proposed to have a similar function in arthropods. However, the effect of octopamine on aggressive behavior is little understood.
An automated video analysis of aggression in male Drosophila has been developed, rendering aggression accessible to high-throughput studies. The software detects the lunge, a conspicuous behavioral act unique to aggression. In lunging, the aggressor rears up on his hind legs and snaps down on his opponent. By using the software to eliminate confounding effects, we now show that aggression is almost abolished in mutant males lacking octopamine. This suppression is independent of whether tyramine, the precursor of octopamine, is increased or also depleted. Restoring octopamine synthesis in the brain either throughout life or in adulthood leads to a partial rescue of aggression. Finally, neuronal silencing of octopaminergic and tyraminergic neurons almost completely abolishes lunges.
Octopamine modulates Drosophila aggression. Genetically depleting the animal of octopamine downregulates lunge frequency without a sizable effect on the lunge motor program. This study provides access to the neuronal circuitry mediating this modulation.
Current Biology 03/2008; 18(3):159-67. · 9.65 Impact Factor
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ABSTRACT: In the eye, visual information is segregated into modalities such as color and motion, these being transferred to the central brain through separate channels. Here, we genetically dissect the achromatic motion channel in the fly Drosophila melanogaster at the level of the first relay station in the brain, the lamina, where it is split into four parallel pathways (L1-L3, amc/T1). The functional relevance of this divergence is little understood. We now show that the two most prominent pathways, L1 and L2, together are necessary and largely sufficient for motion-dependent behavior. At high pattern contrast, the two pathways are redundant. At intermediate contrast, they mediate motion stimuli of opposite polarity, L2 front-to-back, L1 back-to-front motion. At low contrast, L1 and L2 depend upon each other for motion processing. Of the two minor pathways, amc/T1 specifically enhances the L1 pathway at intermediate contrast. L3 appears not to contribute to motion but to orientation behavior.
Neuron 11/2007; 56(1):155-70. · 14.74 Impact Factor
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ABSTRACT: Physical traces underlying simple memories can be confined to a single group of cells in the brain. In the fly Drosophila melanogaster, the Kenyon cells of the mushroom bodies house traces for both appetitive and aversive odor memories. The adenylate cyclase protein, Rutabaga, has been shown to mediate both traces. Here, we show that, for appetitive learning, another group of cells can additionally accommodate a Rutabaga-dependent memory trace. Localized expression of rutabaga in either projection neurons, the first-order olfactory interneurons, or in Kenyon cells, the second-order interneurons, is sufficient for rescuing the mutant defect in appetitive short-term memory. Thus, appetitive learning may induce multiple memory traces in the first- and second-order olfactory interneurons using the same plasticity mechanism. In contrast, aversive odor memory of rutabaga is rescued selectively in the Kenyon cells, but not in the projection neurons. This difference in the organization of memory traces is consistent with the internal representation of reward and punishment.
Journal of Neuroscience 11/2007; 27(41):11132-8. · 7.11 Impact Factor
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ABSTRACT: Neuronal synaptobrevin (n-Syb, alias VAMP2), a synaptic vesicle membrane protein with a central role in neurotransmission, is specifically cleaved by the light chain of tetanus neurotoxin (TNT) that is known to reliably block neuroexocytosis. Here, we study fly photoreceptors transmitting continuous, graded signals to first order interneurons in the lamina, and report consequences of targeted expression of TNT in these cells using the UAS/GAL4 driver/effector system. Expressing the toxin throughout photoreceptor development causes developmental, electrophysiological, and behavioral defects. These can be differentiated by confining toxin expression to shorter developmental periods. Applying a method for controlled temporal and spatial TNT expression, we found that in the early pupa it impaired the development of the retina; in the midpupa, during synapse formation TNT caused a severe hypoplasia of the lamina that persisted into adulthood and left the photoreceptor-interneuron synapses of the lamina without function. Finally, during adulthood TNT neither blocks synaptic transmission in photoreceptors nor depletes the cells of n-Syb. Our study suggests a novel, cell type-specific function of n-Syb in synaptogenesis and it distinguishes between two synapse types: TNT resistant and TNT sensitive ones. These results need to be taken into account if TNT is used for neural circuit analysis.
Journal of Neurobiology 11/2006; 66(12):1271-84. · 3.05 Impact Factor
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ABSTRACT: The GAL4/UAS gene expression system in Drosophila has been crucial in revealing the behavioral significance of neural circuits. Transgene products that block neurotransmitter release and induce cell death have been proved to inhibit neural function powerfully. Here we compare the action of the five effector genes shibire(ts1), Tetanus toxin light chain (TNT), reaper, Diphtheria toxin A-chain (DTA), and inwardly rectifying potassium channel (Kir2.1) and show differences in their efficiency depending on the target cells and the timing of induction. Specifically, effectors blocking neuronal transmission or excitability led to adult-induced paralysis more efficiently than those causing cell ablation. We contrasted these differential potencies in adult to their actions during development. Furthermore, we induced TNT expression in the adult mushroom bodies. In contrast to the successful impairment in short-term olfactory memory by shibire(ts1), adult TNT expression in the same set of cells did not lead to any obvious impairment. Altogether, the efficiency of effector genes depends on properties of the targeted neurons. Thus, we conclude that the selection of the appropriate effector gene is critical for evaluating the function of neural circuits.
The Journal of Comparative Neurology 10/2006; 498(2):194-203. · 3.81 Impact Factor
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ABSTRACT: The fly Drosophila melanogaster can discriminate and remember visual landmarks. It analyses selected parts of its visual environment according to a small number of pattern parameters such as size, colour or contour orientation, and stores particular parameter values. Like humans, flies recognize patterns independently of the retinal position during acquisition of the pattern (translation invariance). Here we show that the central-most part of the fly brain, the fan-shaped body, contains parts of a network mediating visual pattern recognition. We have identified short-term memory traces of two pattern parameters--elevation in the panorama and contour orientation. These can be localized to two groups of neurons extending branches as parallel, horizontal strata in the fan-shaped body. The central location of this memory store is well suited to mediate translational invariance.
Nature 03/2006; 439(7076):551-6. · 36.28 Impact Factor
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ABSTRACT: In the fly Drosophila melanogaster, new genetic, physiological, molecular and behavioral techniques for the functional analysis of the brain are rapidly accumulating. These diverse investigations on the function of the insect brain use gene expression patterns that can be visualized and provide the means for manipulating groups of neurons as a common ground. To take advantage of these patterns one needs to know their typical anatomy.
This paper describes the Virtual Insect Brain (VIB) protocol, a script suite for the quantitative assessment, comparison, and presentation of neuroanatomical data. It is based on the 3D-reconstruction and visualization software Amira, version 3.x (Mercury Inc.) 1. Besides its backbone, a standardization procedure which aligns individual 3D images (series of virtual sections obtained by confocal microscopy) to a common coordinate system and computes average intensities for each voxel (volume pixel) the VIB protocol provides an elaborate data management system for data administration. The VIB protocol facilitates direct comparison of gene expression patterns and describes their interindividual variability. It provides volumetry of brain regions and helps to characterize the phenotypes of brain structure mutants. Using the VIB protocol does not require any programming skills since all operations are carried out at an intuitively usable graphical user interface. Although the VIB protocol has been developed for the standardization of Drosophila neuroanatomy, the program structure can be used for the standardization of other 3D structures as well.
Standardizing brains and gene expression patterns is a new approach to biological shape and its variability. The VIB protocol provides a first set of tools supporting this endeavor in Drosophila. The script suite is freely available at http://www.neurofly.de2.
BMC Bioinformatics 02/2006; 7:544. · 2.75 Impact Factor
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ABSTRACT: Abstract
Background
In the fly Drosophila melanogaster , new genetic, physiological, molecular and behavioral techniques for the functional analysis of the brain are rapidly accumulating. These diverse investigations on the function of the insect brain use gene expression patterns that can be visualized and provide the means for manipulating groups of neurons as a common ground. To take advantage of these patterns one needs to know their typical anatomy.
Results
This paper describes the Virtual Insect Brain (VIB) protocol, a script suite for the quantitative assessment, comparison, and presentation of neuroanatomical data. It is based on the 3D-reconstruction and visualization software Amira, version 3.x (Mercury Inc.) 1 . Besides its backbone, a standardization procedure which aligns individual 3D images (series of virtual sections obtained by confocal microscopy) to a common coordinate system and computes average intensities for each voxel (volume pixel) the VIB protocol provides an elaborate data management system for data administration. The VIB protocol facilitates direct comparison of gene expression patterns and describes their interindividual variability. It provides volumetry of brain regions and helps to characterize the phenotypes of brain structure mutants. Using the VIB protocol does not require any programming skills since all operations are carried out at an intuitively usable graphical user interface. Although the VIB protocol has been developed for the standardization of Drosophila neuroanatomy, the program structure can be used for the standardization of other 3D structures as well.
Conclusion
Standardizing brains and gene expression patterns is a new approach to biological shape and its variability. The VIB protocol provides a first set of tools supporting this endeavor in Drosophila . The script suite is freely available at http://www.neurofly.de 2
BMC Bioinformatics. 01/2006;
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ABSTRACT: The elaboration of neuronal axons and dendrites is dependent on a functional cytoskeleton. Cytoskeletal components have been shown to play a major role in the maintenance of the nervous system through adulthood, and changes in neurofilaments and microtubule-associated proteins (MAPs) have been linked to a variety of neurodegenerative diseases. Here we show that Futsch, the fly homolog of MAP1B, is involved in progressive neurodegeneration. Although Futsch is widely expressed throughout the CNS, degeneration in futsch(olk) primarily occurs in the olfactory system and mushroom bodies. Consistent with the predicted function of Futsch, we find abnormalities in the microtubule network and defects in axonal transport. Degeneration in the adult brain is preceded by learning deficits, revealing a neuronal dysfunction before detectable levels of cell death. Futsch is negatively regulated by the Drosophila Fragile X mental retardation gene, and a mutation in this gene delays the onset of neurodegeneration in futsch(olk). A similar effect is obtained by expression of either fly or bovine tau, suggesting a certain degree of functional redundancy of MAPs. The futsch(olk) mutants exhibit several characteristics of human neurodegenerative diseases, providing an opportunity to study the role of MAPs in progressive neurodegeneration within an experimentally accessible, in vivo model system.
Molecular Biology of the Cell 06/2005; 16(5):2433-42. · 4.94 Impact Factor
