Leibniz Institute of Neurobiology

Magdeburg, Germany

Leibniz Institute of Neurobiology

Magdeburg, Germany

Time filter

Source Type

Bose T.,Leibniz Institute of Neurobiology | Cieslar-Pobuda A.,Linköping University | Cieslar-Pobuda A.,Silesian University of Technology | Wiechec E.,Linköping University
Cell Death and Disease | Year: 2015

Ion channels are abundantly expressed in both excitable and non-excitable cells, thereby regulating the Ca2+ influx and downstream signaling pathways of physiological processes. The immune system is specialized in the process of cancer cell recognition and elimination, and is regulated by different ion channels. In comparison with the immune cells, ion channels behave differently in cancer cells by making the tumor cells more hyperpolarized and influence cancer cell proliferation and metastasis. Therefore, ion channels comprise an important therapeutic target in anti-cancer treatment. In this review, we discuss the implication of ion channels in regulation of Ca2+ homeostasis during the crosstalk between immune and cancer cell as well as their role in cancer progression. © 2015 Macmillan Publishers Limited. All rights reserved.


PubMed | Silesian University of Technology, Leibniz Institute of Neurobiology and Linköping University
Type: | Journal: Cell death & disease | Year: 2015

Ion channels are abundantly expressed in both excitable and non-excitable cells, thereby regulating the Ca(2+) influx and downstream signaling pathways of physiological processes. The immune system is specialized in the process of cancer cell recognition and elimination, and is regulated by different ion channels. In comparison with the immune cells, ion channels behave differently in cancer cells by making the tumor cells more hyperpolarized and influence cancer cell proliferation and metastasis. Therefore, ion channels comprise an important therapeutic target in anti-cancer treatment. In this review, we discuss the implication of ion channels in regulation of Ca(2+) homeostasis during the crosstalk between immune and cancer cell as well as their role in cancer progression.


PubMed | Ludwig Maximilians University of Munich, Leibniz Institute of Neurobiology, Max Planck Institute of Neurobiology, University of Würzburg and Tohoku University
Type: Journal Article | Journal: PloS one | Year: 2015

Electric shock is a common stimulus for nociception-research and the most widely used reinforcement in aversive associative learning experiments. Yet, nothing is known about the mechanisms it recruits at the periphery. To help fill this gap, we undertook a genome-wide association analysis using 38 inbred Drosophila melanogaster strains, which avoided shock to varying extents. We identified 514 genes whose expression levels and/ or sequences co-varied with shock avoidance scores. We independently scrutinized 14 of these genes using mutants, validating the effect of 7 of them on shock avoidance. This emphasizes the value of our candidate gene list as a guide for follow-up research. In addition, by integrating our association results with external protein-protein interaction data we obtained a shock avoidance-associated network of 38 genes. Both this network and the original candidate list contained a substantial number of genes that affect mechanosensory bristles, which are hair-like organs distributed across the flys body. These results may point to a potential role for mechanosensory bristles in shock sensation. Thus, we not only provide a first list of candidate genes for shock avoidance, but also point to an interesting new hypothesis on nociceptive mechanisms.


Malatynska E.,Lilly Research Labs Lilly Corporate Center | Steinbusch H.W.M.,Maastricht University | Redkozubova O.,Russian Academy of Sciences | Bolkunov A.,Russian Academy of Sciences | And 5 more authors.
Experimental Gerontology | Year: 2012

The prevalence of depression increases with aging. We hypothesized that like humans, old animals exhibit anhedonic-like behavior, along with signs of behavioral despair. In rodents, anhedonia, a reduced sensitivity to reward, which is listed as a core feature of major depression in the DSM-IVR, can be measured by a decrease in intake of and preference for sweet solutions. Here, sucrose intake, forced swimming, immobility in the modified tail suspension test, novelty exploration, grooming, anxiety and locomotor activity were compared in naïve 3- and 18-month-old male C57BL/6 mice. The absolute amounts and the ratio of consumed 1% sucrose solution to water intake was significantly smaller in 18-month-old mice than in 3-month-old mice. The consumption of 5%-sucrose solution requiring high levels of drinking effort, novelty exploration in two setups and grooming behavior in the splash test were reduced in older animals. Analysis of other behaviors suggested that the above-mentioned signs of anhedonic-like traits were unlikely to be attributable to the potential effect of aging on metabolic needs for water, taste perception, motor capabilities or the induction of essential anxiety and neophobia. A 4-week treatment with the antidepressant imipramine (7. mg/kg/day) or dimebon, a compound with suggested neuroprotective proneurogenic properties (1. mg/kg/day) restored sucrose intake and preference in 18-month-old mice. Meanwhile, young and old mice showed no differences in the parameters of behavioral despair evaluated in the forced swim and modified tail suspension tests. Thus, the behavioral profile of aged mice parallels that of humans with elderly depression, in whom the symptoms of hedonic deficits typically outweigh affective disturbances. The assessment of anhedonic-like traits with the sucrose preference test in 18-month-old mice will be useful in preclinical studies of elderly depression. © 2012 Elsevier Inc.


Biermann B.,Leibniz Institute of Neurobiology | Biermann B.,University of Munster | Sokoll S.,Leibniz Institute of Neurobiology | Klueva J.,Leibniz Institute of Neurobiology | And 5 more authors.
Nature Communications | Year: 2014

Organization of signalling molecules in biological membranes is crucial for cellular communication. Many receptors, ion channels and cell adhesion molecules are associated with proteins important for their trafficking, surface localization or function. These complexes are embedded in a lipid environment of varying composition. Binding affinities and stoichiometry of such complexes were so far experimentally accessible only in isolated systems or monolayers of cell culture. Visualization of molecular dynamics within signalling complexes and their correlation to specialized membrane compartments demand high temporal and spatial resolution and has been difficult to demonstrate in complex tissue like brain slices. Here we demonstrate the feasibility of single-particle tracking (SPT) in organotypic brain slices to measure molecular dynamics of lipids and transmembrane proteins in correlation to synaptic membrane compartments. This method will provide important information about the dynamics and organization of surface molecules in the complex environment of neuronal networks within brain slices. © 2014 Macmillan Publishers Limited. All rights reserved.


Mayer L.R.,Johannes Gutenberg University Mainz | Diegelmann S.,University of Würzburg | Diegelmann S.,Leibniz Institute of Neurobiology | Abassi Y.,Johannes Gutenberg University Mainz | And 4 more authors.
Fly | Year: 2013

Reporter gene activity in enhancer trap lines is often implicitly assumed to mirror quite faithfully the endogenous expression of the "trapped" gene, even though there are numerous examples of enhancer trap infidelity. optomotor-blind (omb) is a 160 kb gene in which 16 independent P-element enhancer trap insertions of three different types have been mapped in a range of more than 60 kb. We have determined the expression pattern of these elements in wing, eye-antennal and leg imaginal discs as well as in the pupal tergites. We noted that one pGawB insertion (ombP4) selectively failed to report parts of the omb pattern even though the missing pattern elements were apparent in all other 15 lines. We ruled out that ombP4 was defective in the Gal4 promoter region or had inactivated genomic enhancers in the integration process. We propose that the Gal4 reporter gene in pGawB may be sensitive to orientation or promoter proximity effects. © 2013 Landes Bioscience.


Meyer A.F.,University of Oldenburg | Diepenbrock J.-P.,Leibniz Institute of Neurobiology | Ohl F.W.,Leibniz Institute of Neurobiology | Ohl F.W.,Otto Von Guericke University of Magdeburg | Anemuller J.,University of Oldenburg
International IEEE/EMBS Conference on Neural Engineering, NER | Year: 2013

Neurons integrating sensory stimulus features are found in many brain areas up to cortical level, and their understanding is essential for building and improving neural prostheses. Here, we focus on auditory neural coding in the inferior colliculus (IC). Much work has been conducted to identify the primary spectro-temporal sound features. However, a description of how reliable these features are encoded at IC level remains an open question. In a simplified model, the encoding process can be described by a linear integrator followed by a threshold nonlinearity that creates a binary spike sequence. To account for variability in neural responses, coding noise has to be taken into account. However, coding noise reduces the certainty about the stimulus features encoded. Traditional approaches to quantify the amount of noise based on information theory are prone to sampling bias and cannot be bounded in a simply way, making it hard to interpret the results obtained and to compare them across neural populations. Here, we reformulate neural coding as a spike detection task and show that methods from signal detection theory allow an alternative description to quantify coding noise. Using neural responses from the IC in Mongolian gerbils to acoustic stimuli, we demonstrate that this approach allows a reliable description of neural coding noise, particularly in the small data limit, while being highly correlated with information-theoretic quantities in the large-data regime. © 2013 IEEE.


Neupert C.,University of Munster | Schneider R.,Leibniz Institute of Neurobiology | Klatt O.,University of Munster | Klatt O.,Leibniz Institute of Neurobiology | And 8 more authors.
Journal of Neuroscience | Year: 2015

Synapses depend on trafficking of key membrane proteins by lateral diffusion from surface populations and by exocytosis from intracellular pools. The cell adhesion molecule neurexin (Nrxn) plays essential roles in synapses, but the dynamics and regulation of its trafficking are unknown. Here, we performed single-particle tracking and live imaging of transfected, epitope-tagged Nrxn variants in cultured rat and mouse wild-type or knock-out neurons. We observed that structurally larger αNrxn molecules are more mobile in the plasma membrane than smaller βNrxns because αNrxns displayed higher diffusion coefficients in extrasynaptic regions and excitatory or inhibitory terminals. We found that well characterized interactions with extracellular binding partners regulate the surface mobility of Nrxns. Binding to neurexophilin-1 (Nxph1) reduced the surface diffusion of αNrxns when both molecules were coexpressed. Conversely, impeding other interactions by insertion of splice sequence #4 or removal of extracellular Ca2+ augmented the mobility of αNrxns and βNrxns. We also determined that fast axonal transport delivers Nrxns to the neuronal surface because Nrxns comigrate as cargo on synaptic vesicle protein transport vesicles (STVs). Unlike surface mobility, intracellular transport of βNrxn+ STVs was faster than that of αNrxns, but both depended on the microtubule motor protein KIF1A and neuronal activity regulated the velocity. Large spontaneous fusion of Nrxn+ STVs occurred simultaneously with synaptophysin on axonal membranes mostly outside of active presynaptic terminals. Surface Nrxns enriched at synaptic terminals where αNrxns and Nxph1/αNrxns recruited GABAAR subunits. Therefore, our results identify regulated dynamic trafficking as an important property of Nrxns that corroborates their function at synapses. © 2015, the authors.


PubMed | Leibniz Institute of Neurobiology and University of Munster
Type: Journal Article | Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience | Year: 2015

Synapses depend on trafficking of key membrane proteins by lateral diffusion from surface populations and by exocytosis from intracellular pools. The cell adhesion molecule neurexin (Nrxn) plays essential roles in synapses, but the dynamics and regulation of its trafficking are unknown. Here, we performed single-particle tracking and live imaging of transfected, epitope-tagged Nrxn variants in cultured rat and mouse wild-type or knock-out neurons. We observed that structurally larger Nrxn molecules are more mobile in the plasma membrane than smaller Nrxns because Nrxns displayed higher diffusion coefficients in extrasynaptic regions and excitatory or inhibitory terminals. We found that well characterized interactions with extracellular binding partners regulate the surface mobility of Nrxns. Binding to neurexophilin-1 (Nxph1) reduced the surface diffusion of Nrxns when both molecules were coexpressed. Conversely, impeding other interactions by insertion of splice sequence #4 or removal of extracellular Ca(2+) augmented the mobility of Nrxns and Nrxns. We also determined that fast axonal transport delivers Nrxns to the neuronal surface because Nrxns comigrate as cargo on synaptic vesicle protein transport vesicles (STVs). Unlike surface mobility, intracellular transport of Nrxn(+) STVs was faster than that of Nrxns, but both depended on the microtubule motor protein KIF1A and neuronal activity regulated the velocity. Large spontaneous fusion of Nrxn(+) STVs occurred simultaneously with synaptophysin on axonal membranes mostly outside of active presynaptic terminals. Surface Nrxns enriched at synaptic terminals where Nrxns and Nxph1/Nrxns recruited GABAAR subunits. Therefore, our results identify regulated dynamic trafficking as an important property of Nrxns that corroborates their function at synapses.Synapses mediate most functions in our brains and depend on the precise and timely delivery of key molecules throughout life. Neurexins (Nrxns) are essential synaptic cell adhesion molecules that are involved in synaptic transmission and differentiation of synaptic contacts. In addition, Nrxns have been linked to neuropsychiatric diseases such as autism. Because little is known about the dynamic aspects of trafficking of neurexins to synapses, we investigated this important question using single-molecule tracking and time-lapse imaging. We identify distinct differences between major Nrxn variants both in surface mobility and during intracellular transport. Because their dynamic behavior is highly regulated, for example, by different binding activities, these processes have immediate consequences for the function of Nrxns at synapses.


PubMed | Otto Von Guericke University of Magdeburg, Leibniz Institute of Neurobiology, Innsbruck Medical University and University of Munster
Type: Journal Article | Journal: Neurophotonics | Year: 2016

High voltage gated calcium channels (VGCCs) are composed of at least three subunits, one pore forming [Formula: see text]-subunit, an intracellular [Formula: see text]-variant, and a mostly extracellular [Formula: see text]-variant. Interactions between these subunits determine the kinetic properties of VGCCs. It is unclear whether these interactions are stable over time or rather transient. Here, we used single-molecule tracking to investigate the surface diffusion of [Formula: see text]- and [Formula: see text]-subunits at the cell surface. We found that [Formula: see text]-subunits show higher surface mobility than [Formula: see text]-subunits, and that they are only transiently confined together, suggesting a weak association between [Formula: see text]- and [Formula: see text]-subunits. Moreover, we observed that different [Formula: see text]-subunits engage in different degrees of association with the [Formula: see text]-subunit, revealing the tighter interaction of [Formula: see text] with [Formula: see text]. These data indicate a distinct regulation of the [Formula: see text] interaction in VGCC subtypes. We modeled their membrane dynamics in a Monte Carlo simulation using experimentally determined diffusion constants. Our modeling predicts that the ratio of associated [Formula: see text]- and [Formula: see text]-subunits mainly depends on their expression density and confinement in the membrane. Based on the different motilities of particular [Formula: see text]-subunit combinations, we propose that their dynamic assembly and disassembly represent an important mechanism to regulate the signaling properties of VGCC.

Loading Leibniz Institute of Neurobiology collaborators
Loading Leibniz Institute of Neurobiology collaborators