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Biomedical subjects

Martin Heisenberg

Publications and source records attributed to Martin Heisenberg.

At least 19 recordsLinked to original sources
PubMed2006

The Virtual Insect Brain protocol: creating and comparing standardized neuroanatomy.

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.de2.

Animals↗
PubMed2006

Differential potencies of effector genes in adult Drosophila.

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.

Animals↗
PubMed2006

Distinct memory traces for two visual features in the Drosophila brain.

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.

Adenylyl Cyclases↗
PubMed2006

Distinct functions of neuronal synaptobrevin in developing and mature fly photoreceptors.

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.

Animals↗
PubMed2005

Disruption of the MAP1B-related protein FUTSCH leads to changes in the neuronal cytoskeleton, axonal transport defects, and progressive neurodegeneration in Drosophila.

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.

Animals↗
PubMed2005

The carrot, not the stick: appetitive rather than aversive gustatory stimuli support associative olfactory learning in individually assayed Drosophila larvae.

The ability to learn is universal among animals; we investigate associative learning between odors and "tastants" in larval Drosophila melanogaster. As biologically important gustatory stimuli, like sugars, salts, or bitter substances have many behavioral functions, we investigate not only their reinforcing function, but also their response-modulating and response-releasing function. Concerning the response-releasing function, larvae are attracted by fructose and repelled by sodium chloride and quinine; also, fructose increases, but salt and quinine suppress feeding. However, none of these stimuli has a nonassociative, modulatory effect on olfactory choice behavior. Finally, only fructose but neither salt nor quinine has a reinforcing effect in associative olfactory learning. This implies that the response-releasing, response-modulating and reinforcing functions of these tastants are dissociated on the behavioral level. These results open the door to analyze how this dissociation is brought about on the cellular and molecular level; this should be facilitated by the cellular simplicity and genetic accessibility of the Drosophila larva.

Animals↗
PubMed2004

The S6KII (rsk) gene of Drosophila melanogaster differentially affects an operant and a classical learning task.

In an attempt to dissect classical and operant conditioning in Drosophila melanogaster, we have isolated the gene for ribosomal S6 kinase II (S6KII). This enzyme is part of a family of serine-threonine kinases that in mammals have been implicated in the MAPK (mitogen-activated protein kinase) signaling cascade controlling (among other processes) synaptic plasticity (long-term potentiation/long-term depression) and memory formation. The human homolog rsk2 has been linked to mental retardation (Coffin-Lowry syndrome). Mutant analysis in Drosophila shows that S6KII serves different functions in operant place learning and classical (pavlovian) olfactory conditioning. Whereas in the null mutant only pavlovian olfactory learning is affected, a P-element insertion mutant reducing the amount of S6KII only affects operant place learning. A mutant lacking part of the N-terminal kinase domain and performing poorly in both learning tasks is dominant in the operant paradigm and recessive in the pavlovian paradigm. The behavioral defects in the pavlovian task can be rescued by the genomic S6KII transgene. Overexpression of S6KII in wild type has a dominant-negative effect on the operant task that is rescued by the null mutant, whereas in the pavlovian task overexpression may even enhance learning performance.

Animals↗
PubMed2004

Identification of mushroom body miniature, a zinc-finger protein implicated in brain development of Drosophila.

The mushroom bodies are bilaterally arranged structures in the protocerebrum of Drosophila and most other insect species. Mutants with altered mushroom body structure have been instrumental not only in establishing their role in distinct behavioral functions but also in identifying the molecular pathways that control mushroom body development. The mushroom body miniature(1) (mbm(1)) mutation results in grossly reduced mushroom bodies and odor learning deficits in females. With a survey of genomic rescue constructs, we have pinpointed mbm(1) to a single transcription unit and identified a single nucleotide exchange in the 5' untranslated region of the corresponding transcript resulting in a reduced expression of the protein. The most obvious feature of the Mbm protein is a pair of C(2)HC zinc fingers, implicating a function of the protein in binding nucleic acids. Immunohistochemical analysis shows that expression of the Mbm protein is not restricted to the mushroom bodies. BrdUrd labeling experiments indicate a function of Mbm in neuronal precursor cell proliferation.

5' Untranslated Regions↗
PubMed2004

Experimental psychology: event timing turns punishment to reward.

Can relief from pain be a pleasure? If so, noxious events should--despite their typically aversive effects--also have a 'rewarding' after-effect. Through training fruitflies by using an electric shock paired with an odour, we show here that the shock can condition either avoidance of this odour or approach to it. These opposing behaviours depend on the relative timing of the shock and odour presentations during training, and indicate that a shock can act as either an aversive reinforcer or an appetitive one.

Animals↗
PubMed2004

Visual pattern recognition in Drosophila is invariant for retinal position.

Vision relies on constancy mechanisms. Yet, these are little understood, because they are difficult to investigate in freely moving organisms. One such mechanism, translation invariance, enables organisms to recognize visual patterns independent of the region of their visual field where they had originally seen them. Tethered flies (Drosophila melanogaster) in a flight simulator can recognize visual patterns. Because their eyes are fixed in space and patterns can be displayed in defined parts of their visual field, they can be tested for translation invariance. Here, we show that flies recognize patterns at retinal positions where the patterns had not been presented before.

Animals↗
PubMed2004

An engram found? Evaluating the evidence from fruit flies.

Is it possible to localize a memory trace to a subset of cells in the brain? If so, it should be possible to show: first, that neuronal plasticity occurs in these cells. Second, that neuronal plasticity in these cells is sufficient for memory. Third, that neuronal plasticity in these cells is necessary for memory. Fourth, that memory is abolished if these cells cannot provide output during testing. And fifth, that memory is abolished if these cells cannot receive input during training. With regard to olfactory learning in flies, we argue that the notion of the olfactory memory trace being localized to the Kenyon cells of the mushroom bodies is a reasonable working hypothesis.

Animals↗
PubMed2004

Flies lacking all synapsins are unexpectedly healthy but are impaired in complex behaviour.

Vertebrate synapsins are abundant synaptic vesicle phosphoproteins that have been proposed to fine-regulate neurotransmitter release by phosphorylation-dependent control of synaptic vesicle motility. However, the consequences of a total lack of all synapsin isoforms due to a knock-out of all three mouse synapsin genes have not yet been investigated. In Drosophila a single synapsin gene encodes several isoforms and is expressed in most synaptic terminals. Thus the targeted deletion of the synapsin gene of Drosophila eliminates the possibility of functional knock-out complementation by other isoforms. Unexpectedly, synapsin null mutant flies show no obvious defects in brain morphology, and no striking qualitative changes in behaviour are observed. Ultrastructural analysis of an identified 'model' synapse of the larval nerve muscle preparation revealed no difference between wild-type and mutant, and spontaneous or evoked excitatory junction potentials at this synapse were normal up to a stimulus frequency of 5 Hz. However, when several behavioural responses were analysed quantitatively, specific differences between mutant and wild-type flies are noted. Adult locomotor activity, optomotor responses at high pattern velocities, wing beat frequency, and visual pattern preference are modified. Synapsin mutant flies show faster habituation of an olfactory jump response, enhanced ethanol tolerance, and significant defects in learning and memory as measured using three different paradigms. Larval behavioural defects are described in a separate paper. We conclude that Drosophila synapsins play a significant role in nervous system function, which is subtle at the cellular level but manifests itself in complex behaviour.

Action Potentials↗
PubMed2004

The DrosDel collection: a set of P-element insertions for generating custom chromosomal aberrations in Drosophila melanogaster.

We describe a collection of P-element insertions that have considerable utility for generating custom chromosomal aberrations in Drosophila melanogaster. We have mobilized a pair of engineered P elements, p[RS3] and p[RS5], to collect 3243 lines unambiguously mapped to the Drosophila genome sequence. The collection contains, on average, an element every 35 kb. We demonstrate the utility of the collection for generating custom chromosomal deletions that have their end points mapped, with base-pair resolution, to the genome sequence. The collection was generated in an isogenic strain, thus affording a uniform background for screens where sensitivity to genetic background is high. The entire collection, along with a computational and genetic toolbox for designing and generating custom deletions, is publicly available. Using the collection it is theoretically possible to generate >12,000 deletions between 1 bp and 1 Mb in size by simple eye color selection. In addition, a further 37,000 deletions, selectable by molecular screening, may be generated. We are now using the collection to generate a second-generation deficiency kit that is precisely mapped to the genome sequence.

Animals↗
PubMed2003

Dopamine and octopamine differentiate between aversive and appetitive olfactory memories in Drosophila.

The catecholamines play a major role in the regulation of behavior. Here we investigate, in the fly Drosophila melanogaster, the role of dopamine and octopamine (the presumed arthropod homolog of norepinephrine) during the formation of appetitive and aversive olfactory memories. We find that for the formation of both types of memories, cAMP signaling is necessary and sufficient within the same subpopulation of mushroom-body intrinsic neurons. On the other hand, memory formation can be distinguished by the requirement for different catecholamines, dopamine for aversive and octopamine for appetitive conditioning. Our results suggest that in associative conditioning, different memories are formed of the same odor under different circumstances, and that they are linked to the respective motivational systems by their specific modulatory pathways.

Animals↗
PubMed2002

Extinction antagonizes olfactory memory at the subcellular level.

Memory loss occurs by diverse mechanisms, as different time constants of performance decrement and sensitivities to experimental manipulations suggest. While the phenomena of memory decay, interference, and extinction are well established behaviorally, little is known about them at the circuit or molecular level. In Drosophila, odorant memories lasting up to 3 hr can be localized to mushroom body Kenyon cells, a single neuronal level in the olfactory pathway. The plasticity underlying this memory trace can be induced without Kenyon cell synaptic output. Experimental extinction, i.e., presentation of the conditioned stimulus without the reinforcer, reduces memory performance and does so at the same circuit level as memory formation. Thus, unreinforced presentation of learned odorants antagonizes intracellularly the signaling cascade underlying memory formation.

Animals↗