Leibniz Institute For Neurobiologie Lin

Magdeburg, Germany

Leibniz Institute For Neurobiologie Lin

Magdeburg, Germany
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Kleber J.,Leibniz Institute For Neurobiologie Lin | Chen Y.-C.,Leibniz Institute For Neurobiologie Lin | Michels B.,Leibniz Institute For Neurobiologie Lin | Saumweber T.,Leibniz Institute For Neurobiologie Lin | And 6 more authors.
Learning and Memory | Year: 2016

Synapsin is an evolutionarily conserved presynaptic phosphoprotein. It is encoded by only one gene in the Drosophila genome and is expressed throughout the nervous system. It regulates the balance between reserve and releasable vesicles, is required to maintain transmission upon heavy demand, and is essential for proper memory function at the behavioral level. Task-relevant sensorimotor functions, however, remain intact in the absence of Synapsin. Using an odor-sugar reward associative learning paradigm in larval Drosophila, we show that memory scores in mutants lacking Synapsin (syn97) are lower than in wild-type animals only when more salient, higher concentrations of odor or of the sugar reward are used. Furthermore, we show that Synapsin is selectively required for larval short-term memory. Thus, without Synapsin Drosophila larvae can learn and remember, but Synapsin is required to form memories that match in strength to event salience - in particular to a high saliency of odors, of rewards, or the salient recency of an event. We further show that the residual memory scores upon a lack of Synapsin are not further decreased by an additional lack of the Sap47 protein. In combination with mass spectrometry data showing an up-regulated phosphorylation of Synapsin in the larval nervous system upon a lack of Sap47, this is suggestive of a functional interdependence of Synapsin and Sap47. © 2015 Kleber et al.

Schleyer M.,Leibniz Institute For Neurobiologie Lin | Diegelmann S.,Leibniz Institute For Neurobiologie Lin | Michels B.,Leibniz Institute For Neurobiologie Lin | Saumweber T.,Leibniz Institute For Neurobiologie Lin | And 3 more authors.
Handbook of Behavioral Neuroscience | Year: 2013

The brain is the organ of behavior organization. It structures the solution to the problem of what to do. This is complicated because usually we cannot be certain which behavior would be relatively the best. These processes, taking place between the moment when an uncertainty between behavioral options is recognized and the actual expression of behavior, we regard as 'taking a decision.' Such decision making needs to integrate (1) sensory input, (2) the current status reflecting evolutionary and individual history, (3) the available behavioral options, and (4) their expected outcomes. We focus on the decision to behaviorally express an associative memory trace-or not. After sketching the architecture of the chemobehavioral system in larval Drosophila, we present a working hypothesis of odor-taste associative memory trace formation and then discuss whether outcome expectations contribute to the organization of conditioned behavior. We argue that indeed conditioned olfactory behavior is organized according to its expected outcome, namely toward finding reward or escaping punishment, respectively. Conditioned olfactory behaviors are thus not responsive in nature but, rather, are actions expressed for the sake of the sought-for reward and the attempted relief. In addition to the organization of such outcome expectations, we discuss parametric features ('axes') of behavioral tasks that we believe bear upon the decision character of the underlying process and discuss whether these features can be found, or may reasonably be sought for, in larval Drosophila. It is argued that rather than trying to draw a line between behavioral processes that reflect decisions and those that are not, it is more useful to ask how strong the decision character of a given behavioral faculty is? © 2013 Elsevier B.V.

Niewalda T.,Leibniz Institute For Neurobiologie Lin | Michels B.,Leibniz Institute For Neurobiologie Lin | Jungnickel R.,Leibniz Institute For Neurobiologie Lin | Diegelmann S.,Leibniz Institute For Neurobiologie Lin | And 5 more authors.
Journal of Neuroscience | Year: 2015

Adverse life events can induce two kinds of memory with opposite valence, dependent on timing: “negative” memories for stimuli preceding them and “positive” memories for stimuli experienced at the moment of “relief.” Such punishment memory and relief memory are found in insects, rats, and man. For example, fruit flies (Drosophila melanogaster) avoid an odor after odor-shock training (“forward conditioning” of the odor), whereas after shock-odor training (“backward conditioning” of the odor) they approach it. Do these timing-dependent associative processes share molecular determinants? We focus on the role of Synapsin, a conserved presynaptic phosphoprotein regulating the balance between the reserve pool and the readily releasable pool of synaptic vesicles. We find that a lack of Synapsin leaves task-relevant sensory and motor faculties unaffected. In contrast, both punishment memory and relief memory scores are reduced. These defects reflect a true lessening of associative memory strength, as distortions in nonassociative processing (e.g., susceptibility to handling, adaptation, habituation, sensitization), discrimination ability, and changes in the time course of coincidence detection can be ruled out as alternative explanations. Reductions in punishment- and relief-memory strength are also observed upon an RNAi-mediated knock-down of Synapsin, and are rescued both by acutely restoring Synapsin and by locally restoring it in the mushroom bodies of mutant flies. Thus, both punishment memory and relief memory require the Synapsin protein and in this sense share genetic and molecular determinants. We note that corresponding molecular commonalities between punishment memory and relief memory in humans would constrain pharmacological attempts to selectively interfere with excessive associative punishment memories, e.g., after traumatic experiences. © 2015 the authors.

Niewalda T.,Leibniz Institute For Neurobiologie Lin | Jeske I.,University of Leipzig | Michels B.,Leibniz Institute For Neurobiologie Lin | Gerber B.,Leibniz Institute For Neurobiologie Lin | And 2 more authors.
Biology Open | Year: 2014

Understanding social behaviour requires a study case that is simple enough to be tractable, yet complex enough to remain interesting. Do larval Drosophila meet these requirements? In a broad sense, this question can refer to effects of the mere presence of other larvae on the behaviour of a target individual. Here we focused in a more strict sense on 'peer pressure', that is on the question of whether the behaviour of a target individual larva is affected by what a surrounding group of larvae is doing. We found that innate olfactory preference of a target individual was neither affected (i) by the level of innate olfactory preference in the surrounding group nor (ii) by the expression of learned olfactory preference in the group. Likewise, learned olfactory preference of a target individual was neither affected (iii) by the level of innate olfactory preference of the surrounding group nor (iv) by the learned olfactory preference the group was expressing. We conclude that larval Drosophila thus do not take note of specifically what surrounding larvae are doing. This implies that in a strict sense, and to the extent tested, there is no social interaction between larvae. These results validate widely used en mass approaches to the behaviour of larval Drosophila. © 2014, Company of Biologists Ltd. All rights reserved.

Niewalda T.,University of Würzburg | Niewalda T.,University of Leipzig | Voller T.,University of Würzburg | Voller T.,Visitron Systems GmbH | And 13 more authors.
PLoS ONE | Year: 2011

How do physico-chemical stimulus features, perception, and physiology relate? Given the multi-layered and parallel architecture of brains, the question specifically is where physiological activity patterns correspond to stimulus features and/or perception. Perceived distances between six odour pairs are defined behaviourally from four independent odour recognition tasks. We find that, in register with the physico-chemical distances of these odours, perceived distances for 3-octanol and n-amylacetate are consistently smallest in all four tasks, while the other five odour pairs are about equally distinct. Optical imaging in the antennal lobe, using a calcium sensor transgenically expressed in only first-order sensory or only second-order olfactory projection neurons, reveals that 3-octanol and n-amylacetate are distinctly represented in sensory neurons, but appear merged in projection neurons. These results may suggest that within-antennal lobe processing funnels sensory signals into behaviourally meaningful categories, in register with the physico-chemical relatedness of the odours. © 2011 Niewalda et al.

Gerber B.,Leibniz Institute For Neurobiologie Lin | Gerber B.,Center for Behavioral Brain science | Gerber B.,Otto Von Guericke University of Magdeburg | Yarali A.,Leibniz Institute For Neurobiologie Lin | And 5 more authors.
Learning and Memory | Year: 2014

Memories relating to a painful, negative event are adaptive and can be stored for a lifetime to support preemptive avoidance, escape, or attack behavior. However, under unfavorable circumstances such memories can become overwhelmingly powerful. They may trigger excessively negative psychological states and uncontrollable avoidance of locations, objects, or social interactions. It is therefore obvious that any process to counteract such effects will be of value. In this context, we stress from a basic-research perspective that painful, negative events are "Janus-faced" in the sense that there are actually two aspects about them that are worth remembering: What made them happen and what made them cease. We review published findings from fruit flies, rats, and man showing that both aspects, respectively related to the onset and the offset of the negative event, induce distinct and oppositely valenced memories: Stimuli experienced before an electric shock acquire negative valence as they signal upcoming punishment, whereas stimuli experienced after an electric shock acquire positive valence because of their association with the relieving cessation of pain. We discuss how memories for such punishment- and relief-learning are organized, how this organization fits into the threat-imminence model of defensive behavior, and what perspectives these considerations offer for applied psychology in the context of trauma, panic, and nonsuicidal self-injury. © 2014 Simpson et al.; Published by Cold Spring Harbor Laboratory Press.

Diegelmann S.,Leibniz Institute For Neurobiologie Lin | Klagges B.,University of Leipzig | Michels B.,Leibniz Institute For Neurobiologie Lin | Schleyer M.,Leibniz Institute For Neurobiologie Lin | And 5 more authors.
Journal of Experimental Biology | Year: 2013

Drosophila larvae are focused on feeding and have few neurons. Within these bounds, however, there still are behavioural degrees of freedom. This review is devoted to what these elements of flexibility are, and how they come about. Regarding odour-food associative learning, the emerging working hypothesis is that when a mushroom body neuron is activated as a part of an odour-specific set of mushroom body neurons, and coincidently receives a reinforcement signal carried by aminergic neurons, the AC-cAMP-PKA cascade is triggered. One substrate of this cascade is Synapsin, and therefore this review features a general and comparative discussion of Synapsin function. Phosphorylation of Synapsin ensures an alteration of synaptic strength between this mushroom body neuron and its target neuron(s). If the trained odour is encountered again, the pattern of mushroom body neurons coding this odour is activated, such that their modified output now allows conditioned behaviour. However, such an activated memory trace does not automatically cause conditioned behaviour. Rather, in a process that remains off-line from behaviour, the larvae compare the value of the testing situation (based on gustatory input) with the value of the odour-activated memory trace (based on mushroom body output). The circuit towards appetitive conditioned behaviour is closed only if the memory trace suggests that tracking down the learned odour will lead to a place better than the current one. It is this expectation of a positive outcome that is the immediate cause of appetitive conditioned behaviour. Such conditioned search for reward corresponds to a view of aversive conditioned behaviour as conditioned escape from punishment, which is enabled only if there is something to escape from - much in the same way as we only search for things that are not there, and run for the emergency exit only when there is an emergency. One may now ask whether beyond 'value' additional information about reinforcement is contained in the memory trace, such as information about the kind and intensity of the reinforcer used. The Drosophila larva may allow us to develop satisfyingly detailed accounts of such mnemonic richness - if it exists. © 2013. Published by The Company of Biologists Ltd.

Eschbach C.,University of Würzburg | Cano C.,University of Würzburg | Haberkern H.,University of Würzburg | Schraut K.,University of Würzburg | And 7 more authors.
Journal of Experimental Biology | Year: 2011

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/B4), 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 'bad' events. © 2011. Published by The Company of Biologists Ltd.

PubMed | Otto Von Guericke University of Magdeburg, University of Leipzig, University of Bonn, Leibniz Institute For Neurobiologie Lin and University of Konstanz
Type: Journal Article | Journal: Biology open | Year: 2014

The ability to respond to and to learn about mechanosensory disturbance is widespread among animals. Using Drosophila larvae, we describe how the frequency of mechanosensory disturbance (buzz) affects three aspects of behaviour: free locomotion, innate olfactory preference, and potency as a punishment. We report that (i) during 2-3seconds after buzz onset the larvae slowed down and then turned, arguably to escape this situation; this was seen for buzz frequencies of 10, 100, and 1000Hz, (ii) innate olfactory preference was reduced when tested in the presence of the buzz; this effect was strongest for the 100Hz frequency, (iii) after odour-buzz associative training, we observed escape from the buzz-associated odour; this effect was apparent for 10 and 100, but not for 1000Hz. We discuss the multiple behavioural effects of mechanosensation and stress that the immediate effects on locomotion and the impact as punishment differ in their frequency-dependence. Similar dissociations between immediate, reflexive behavioural effects and reinforcement potency were previously reported for sweet, salty and bitter tastants. It should be interesting to see how these features map onto the organization of sensory, ascending pathways.

PubMed | Leibniz Institute for Molecular Pharmacology, Charité - Medical University of Berlin and Leibniz Institute For Neurobiologie Lin
Type: | Journal: Nature communications | Year: 2015

KCNQ2 (Kv7.2) and KCNQ3 (Kv7.3) K(+) channels dampen neuronal excitability and their functional impairment may lead to epilepsy. Less is known about KCNQ5 (Kv7.5), which also displays wide expression in the brain. Here we show an unexpected role of KCNQ5 in dampening synaptic inhibition and shaping network synchronization in the hippocampus. KCNQ5 localizes to the postsynaptic site of inhibitory synapses on pyramidal cells and in interneurons. Kcnq5(dn/dn) mice lacking functional KCNQ5 channels display increased excitability of different classes of interneurons, enhanced phasic and tonic inhibition, and decreased electrical shunting of inhibitory postsynaptic currents. In vivo, loss of KCNQ5 function leads to reduced fast (gamma and ripple) hippocampal oscillations, altered gamma-rhythmic discharge of pyramidal cells and impaired spatial representations. Our work demonstrates that KCNQ5 controls excitability and function of hippocampal networks through modulation of synaptic inhibition.

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