@article {47538, title = {A screen for constituents of motor control and decision making in Drosophila reveals visual distance-estimation neurons.}, journal = {Scientific Reports}, volume = {6}, year = {2016}, month = {2016}, pages = {27000}, abstract = {

Climbing over chasms larger than step size is vital to fruit flies, since foraging and mating are achieved while walking. Flies avoid futile climbing attempts by processing parallax-motion vision to estimate gap width. To identify neuronal substrates of climbing control, we screened a large collection of fly lines with temporarily inactivated neuronal populations in a novel high-throughput assay described here. The observed climbing phenotypes were classified; lines in each group are reported. Selected lines were further analysed by high-resolution video cinematography. One striking class of flies attempts to climb chasms of unsurmountable width; expression analysis guided us to C2 optic-lobe interneurons. Inactivation of C2 or the closely related C3 neurons with highly specific intersectional driver lines consistently reproduced hyperactive climbing whereas strong or weak artificial depolarization of C2/C3 neurons strongly or mildly decreased climbing frequency. Contrast-manipulation experiments support our conclusion that C2/C3 neurons are part of the distance-evaluation system.

}, issn = {2045-2322}, doi = {10.1038/srep27000}, author = {Triphan, Tilman and Nern, Aljoscha and Roberts, Sonia F and Korff, Wyatt and Naiman, Daniel Q and Strauss, Roland} } @article {46347, title = {Cell types and coincident synapses in the ellipsoid body of Drosophila.}, journal = {The European Journal of Neuroscience}, volume = {39}, year = {2014}, month = {2014 May}, pages = {1586-601}, abstract = {

Cellular ultrastructures for signal integration are unknown in any nervous system. The ellipsoid body (EB) of the Drosophila brain is thought to control locomotion upon integration of various modalities of sensory signals with the animal internal status. However, the expected excitatory and inhibitory input convergence that virtually all brain centres exhibit is not yet described in the EB. Based on the EB expression domains of genetic constructs from the choline acetyl transferase (Cha), glutamic acid decarboxylase (GAD) and tyrosine hydroxylase (TH) genes, we identified a new set of neurons with the characteristic ring-shaped morphology (R\ neurons) which are presumably cholinergic, in addition to the existing GABA-expressing neurons. The R1 morphological subtype is represented in the Cha- and TH-expressing classes. In addition, using transmission electron microscopy, we identified a novel type of synapse in the EB, which exhibits the precise array of two independent active zones over the same postsynaptic dendritic domain, that we named {\textquoteright}agora{\textquoteright}. This array is compatible with a coincidence detector role, and represents ~8\% of all EB synapses in Drosophila. Presumably excitatory R\ neurons contribute to coincident synapses. Functional silencing of EB neurons by driving genetically tetanus toxin expression either reduces walking speed or alters movement orientation depending on the targeted R\ neuron subset, thus revealing functional specialisations in the EB for locomotion control.

}, keywords = {Animals, Animals, Genetically Modified, Bees, Brain, Choline O-Acetyltransferase, Drosophila, Drosophila Proteins, Female, gamma-Aminobutyric Acid, Green Fluorescent Proteins, Male, Microscopy, Electron, Transmission, Nerve Tissue Proteins, Neurons, Orientation, Paired Box Transcription Factors, Synapses, Tetanus Toxin, Transcription Factors, Visual Perception, Walking}, issn = {1460-9568}, doi = {10.1111/ejn.12537}, author = {Mart{\'\i}n-Pe{\~n}a, Alfonso and Acebes, Angel and Rodr{\'\i}guez, Jos{\'e}-Rodrigo and Chevalier, Valerie and Casas-Tinto, Sergio and Triphan, Tilman and Strauss, Roland and Ferr{\'u}s, Alberto} } @article {46346, title = {β-secretase cleavage of the fly amyloid precursor protein is required for glial survival.}, journal = {Journal of Neuroscience}, volume = {32}, year = {2012}, month = {2012 Nov 14}, pages = {16181-92}, abstract = {

β-secretase (or BACE1) is the key enzyme in the production of β-amyloid (Aβ), which accumulates in the senile plaques characteristic for Alzheimer{\textquoteright}s disease. Consequently, the lack of BACE1 prevents β-processing of the amyloid precursor protein and Aβ production, which made it a promising target for drug development. However, the loss of BACE1 is also detrimental, leading to myelination defects and altered neuronal activity, functions that have been associated with the cleavage of Neuregulin and a voltage-gated sodium channel subunit. Here we show that the Drosophila ortholog of BACE, dBACE, is required for glial survival. Cell-specific knockdown experiments reveal that this is a non-cell autonomous function, as a knockdown of dBACE in photoreceptor neurons leads to progressive degeneration of glia in their target zone, the lamina. Interestingly, this phenotype is suppressed by the loss of the fly amyloid precursor protein (APPL), whereas a secretion-deficient form of APPL enhances the degeneration. This shows that full-length APPL in neurons promotes the death of neighboring glial cells and that β-processing of APPL is needed to prevent glial death. These results therefore not only demonstrate a novel function for an APP protein in glia, but they also show this function specifically requires regulation by β-cleavage.

}, keywords = {Amyloid beta-Protein Precursor, Amyloid Precursor Protein Secretases, Animals, Axons, Blotting, Western, Cell Death, Cell Movement, Cell Survival, Drosophila, Immunohistochemistry, Microscopy, Electron, Neuregulins, Neuroglia, Polymerase Chain Reaction, Retina, RNA, RNA Interference, Vacuoles}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.0228-12.2012}, author = {Bolkan, Bonnie J and Triphan, Tilman and Kretzschmar, Doris} } @article {46345, title = {Associative learning between odorants and mechanosensory punishment in larval Drosophila.}, journal = {Journal of Expiremental Biology}, volume = {214}, year = {2011}, month = {2011 Dec 1}, pages = {3897-905}, abstract = {

We tested whether Drosophila larvae can associate odours with a mechanosensory disturbance as a punishment, using substrate vibration conveyed by a loudspeaker (buzz:). One odour (A) was presented with the buzz, while another odour (B) was presented without the buzz (A/B training). Then, animals were offered the choice between A and B. After reciprocal training (A/B), a second experimental group was tested in the same way. We found that larvae show conditioned escape from the previously punished odour. We further report an increase of associative performance scores with the number of punishments, and an increase according to the number of training cycles. Within the range tested (between 50 and 200 Hz), however, the pitch of the buzz does not apparently impact associative success. Last, but not least, we characterized odour-buzz memories with regard to the conditions under which they are behaviourally expressed--or not. In accordance with what has previously been found for associative learning between odours and bad taste (such as high concentration salt or quinine), we report that conditioned escape after odour-buzz learning is disabled if escape is not warranted, i.e. if no punishment to escape from is present during testing. Together with the already established paradigms for the association of odour and bad taste, the present assay offers the prospect of analysing how a relatively simple brain orchestrates memory and behaviour with regard to different kinds of {\textquoteright}bad{\textquoteright} events.

}, keywords = {Animals, Association Learning, Behavior, Animal, Conditioning (Psychology), Drosophila melanogaster, Larva, Mechanotransduction, Cellular, Memory, Odors, Punishment, Sound}, issn = {1477-9145}, doi = {10.1242/jeb.060533}, author = {Eschbach, Claire and Cano, Carmen and Haberkern, Hannah and Schraut, Karla and Guan, Chonglin and Triphan, Tilman and Gerber, Bertram} } @article {2686, title = {Appetitive and aversive visual learning in freely moving Drosophila.}, journal = {Frontiers in Behavioral Neuroscience}, volume = {4}, year = {2010}, month = {2010 Mar 9}, pages = {10}, abstract = {

To compare appetitive and aversive visual memories of the fruit fly Drosophila melanogaster, we developed a new paradigm for classical conditioning. Adult flies are trained en masse to differentially associate one of two visual conditioned stimuli (CS) (blue and green light as CS) with an appetitive or aversive chemical substance (unconditioned stimulus or US). In a test phase, flies are given a choice between the paired and the unpaired visual stimuli. Associative memory is measured based on altered visual preference in the test. If a group of flies has, for example, received a sugar reward with green light in the training, they show a significantly higher preference for the green stimulus during the test than another group of flies having received the same reward with blue light. We demonstrate critical parameters for the formation of visual appetitive memory, such as training repetition, order of reinforcement, starvation, and individual conditioning. Furthermore, we show that formic acid can act as an aversive chemical reinforcer, yielding weak, yet significant, aversive memory. These results provide a basis for future investigations into the cellular and molecular mechanisms underlying visual memory and perception in Drosophila.

}, issn = {1662-5153}, doi = {10.3389/fnbeh.2010.00010}, author = {Schnaitmann, Christopher and Vogt, Katrin and Triphan, Tilman and Tanimoto, Hiromu} } @article {2685, title = {Visual targeting of motor actions in climbing Drosophila.}, journal = {Current Biology}, volume = {20}, year = {2010}, month = {2010 Apr 13}, pages = {663-8}, abstract = {

Drosophila melanogaster flies cross surmountable gaps in their walkway of widths exceeding their body length with an astounding maneuver but avoid attempts at insurmountable gaps by visual width estimation. Different mutant lines affect specific aspects of this maneuver, indicating a high complexity and modularity of the underlying motor control. Here we report on two mutants, ocelliless(1) and tay bridge(1), that, although making a correct decision to climb, fail dramatically in aiming at the right direction. Both mutants show structural defects in the protocerebral bridge, a central complex neuropil formed like a handlebar spanning the brain hemispheres. The bridge has been implicated in step-length control in walking flies and celestial E-vector orientation in locusts. In rescue experiments using tay bridge(1) flies, the integrity of the bridge was reestablished, concomitantly leading to a significant improvement of their orientation at the gap. Although producing directional scatter, their attempts were clearly aimed at the landing site. However, this partial rescue was lost in these flies at a reduced-visibility landing site. We therefore conclude that the protocerebral bridge is an essential part of a visual targeting network that transmits directional clues to the motor output via a known projection system.

}, keywords = {Animals, Biological, Brain, Drosophila melanogaster, Genes, Genetically Modified, Insect, Models, Motor Activity, Mutation, Visual Perception}, issn = {1879-0445}, doi = {10.1016/j.cub.2010.02.055}, author = {Triphan, Tilman and Poeck, Burkhard and Neuser, Kirsa and Strauss, Roland} } @article {2687, title = {Neurotoxic effects induced by the Drosophila amyloid-beta peptide suggest a conserved toxic function.}, journal = {Neurobiology of Disease}, volume = {33}, year = {2009}, month = {2009 Feb}, pages = {274-81}, abstract = {

The accumulation of amyloid-beta (Abeta) into plaques is a hallmark feature of Alzheimer{\textquoteright}s disease (AD). While amyloid precursor protein (APP)-related proteins are found in most organisms, only Abeta fragments from human APP have been shown to induce amyloid deposits and progressive neurodegeneration. Therefore, it was suggested that neurotoxic effects are a specific property of human Abeta. Here we show that Abeta fragments derived from the Drosophila orthologue APPL aggregate into intracellular fibrils, amyloid deposits, and cause age-dependent behavioral deficits and neurodegeneration. We also show that APPL can be cleaved by a novel fly beta-secretase-like enzyme. This suggests that Abeta-induced neurotoxicity is a conserved function of APP proteins whereby the lack of conservation in the primary sequence indicates that secondary structural aspects determine their pathogenesis. In addition, we found that the behavioral phenotypes precede extracellular amyloid deposit formation, supporting results that intracellular Abeta plays a key role in AD.

}, keywords = {Aging, Amino Acid Sequence, Amyloid, Amyloid beta-Protein Precursor, Amyloid Precursor Protein Secretases, Animal, Animals, Apoptosis, Behavior, Blotting, Brain, Cell Surface, Drosophila melanogaster, Drosophila Proteins, Electron, Gene Expression, Immunohistochemistry, Light, Membrane Proteins, Microscopy, Molecular Sequence Data, Nerve Degeneration, Nerve Tissue Proteins, Neurons, Peptide Fragments, Protease Nexins, Receptors, Western}, issn = {1095-953X}, doi = {10.1016/j.nbd.2008.10.014}, author = {Carmine-Simmen, Katia and Proctor, Thomas and Tsch{\"a}pe, Jakob and Poeck, Burkhard and Triphan, Tilman and Strauss, Roland and Kretzschmar, Doris} } @article {2689, title = {Analysis of a spatial orientation memory in Drosophila.}, journal = {Nature}, volume = {453}, year = {2008}, month = {2008 Jun 26}, pages = {1244-7}, abstract = {

Flexible goal-driven orientation requires that the position of a target be stored, especially in case the target moves out of sight. The capability to retain, recall and integrate such positional information into guiding behaviour has been summarized under the term spatial working memory. This kind of memory contains specific details of the presence that are not necessarily part of a long-term memory. Neurophysiological studies in primates indicate that sustained activity of neurons encodes the sensory information even though the object is no longer present. Furthermore they suggest that dopamine transmits the respective input to the prefrontal cortex, and simultaneous suppression by GABA spatially restricts this neuronal activity. Here we show that Drosophila melanogaster possesses a similar spatial memory during locomotion. Using a new detour setup, we show that flies can remember the position of an object for several seconds after it has been removed from their environment. In this setup, flies are temporarily lured away from the direction towards their hidden target, yet they are thereafter able to aim for their former target. Furthermore, we find that the GABAergic (stainable with antibodies against GABA) ring neurons of the ellipsoid body in the central brain are necessary and their plasticity is sufficient for a functional spatial orientation memory in flies. We also find that the protein kinase S6KII (ignorant) is required in a distinct subset of ring neurons to display this memory. Conditional expression of S6KII in these neurons only in adults can restore the loss of the orientation memory of the ignorant mutant. The S6KII signalling pathway therefore seems to be acutely required in the ring neurons for spatial orientation memory in flies.

}, keywords = {90-kDa, Animals, Drosophila melanogaster, gamma-Aminobutyric Acid, Locomotion, Memory, Models, Neurological, Neurons, Orientation, Ribosomal Protein S6 Kinases, Signal Transduction, Space Perception}, issn = {1476-4687}, doi = {10.1038/nature07003}, author = {Neuser, Kirsa and Triphan, Tilman and Mronz, Markus and Poeck, Burkhard and Strauss, Roland} } @article {2688, title = {Locomotor control by the central complex in Drosophila-an analysis of the tay bridge mutant.}, journal = {Developmental Neurobiology}, volume = {68}, year = {2008}, month = {2008 Jul}, pages = {1046-58}, abstract = {

Several aspects of locomotor control have been ascribed to the central complex of the insect brain; however, the role of distinct substructures of this complex is not well known. The tay bridge1 (tay1) mutant of Drosophila melanogaster was originally isolated on the basis of reduced walking speed and activity. In addition, tay1 is defective in the compensation of rotatory stimuli during walking and histologically, tay1 causes a mid-sagittal constriction of the protocerebral bridge, a constituent of the central complex. Cloning of the tay gene revealed that it encodes a novel protein with no significant homology to any known protein. To associate the behavioral phenotypes with the anatomical defect in the protocerebral bridge, we used different driver lines to express the tay cDNA in various neuronal subpopulations of the central brain in tay1-mutant flies. These experiments showed an association of the aberrant walking speed and activity with the structural defect in the protocerebral bridge. In contrast, the compensation of rotatory stimuli during walking was rescued without a restoration of the protocerebral bridge. The results of our differential rescue approach are supported by neuronal silencing experiments using conditional tetanus toxin expression in the same subset of neurons. These findings show for the first time that the walking speed and activity is controlled by different substructures of the central brain than the compensatory locomotion for rotatory stimuli.

}, keywords = {Amino Acid Sequence, Animal, Animals, Behavior, Brain, Cell Line, Drosophila melanogaster, Drosophila Proteins, Genetic Vectors, Locomotion, Male, Motor Activity, Mushroom Bodies, Mutation, Neurons, Phenotype, Photic Stimulation, Polymerase Chain Reaction, Transformed}, issn = {1932-8451}, doi = {10.1002/dneu.20643}, author = {Poeck, Burkhard and Triphan, Tilman and Neuser, Kirsa and Strauss, Roland} }