A5017403142- Neurobiology and Insect Physiology Research
- Cellular transport and secretion
- Photoreceptor and optogenetics research
- Neuroscience and Neuropharmacology Research
- Lipid Membrane Structure and Behavior
- Retinal Development and Disorders
- Receptor Mechanisms and Signaling
- Advanced Fluorescence Microscopy Techniques
- Neuroscience and Neural Engineering
- Plant and Biological Electrophysiology Studies
- Advanced Electron Microscopy Techniques and Applications
- Animal Behavior and Reproduction
- Circadian rhythm and melatonin
- Cell Image Analysis Techniques
- Insect and Arachnid Ecology and Behavior
- Ion channel regulation and function
- Signaling Pathways in Disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Cell Adhesion Molecules Research
- Ion Channels and Receptors
- Characterization and Applications of Magnetic Nanoparticles
- Genetics, Aging, and Longevity in Model Organisms
- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- Physiological and biochemical adaptations
Leipzig University
2009-2024
University of Würzburg
2010-2021
Czech Academy of Sciences, Institute of Physiology
2017-2018
Deutsche Forschungsgemeinschaft
2010
European Neuroscience Institute Göttingen
2005-2007
University of Göttingen
2007
Max Planck Institute for Biophysical Chemistry
2006
Max Planck Society
2005
The molecular organization of presynaptic active zones during calcium influx–triggered neurotransmitter release is the focus intense investigation. Drosophila coiled-coil domain protein Bruchpilot (BRP) was observed in donut-shaped structures centered at neuromuscular synapses by using subdiffraction resolution STED (stimulated emission depletion) fluorescence microscopy. At brp mutant zones, electron-dense projections (T-bars) were entirely lost, Ca 2+ channels reduced density, evoked...
Synaptic vesicles fuse at active zone (AZ) membranes where Ca2+ channels are clustered and that typically decorated by electron-dense projections. Recently, mutants of the Drosophila melanogaster ERC/CAST family protein Bruchpilot (BRP) were shown to lack dense projections (T-bars) suffer from channel–clustering defects. In this study, we used high resolution light microscopy, electron intravital imaging analyze function BRP in AZ assembly. Consistent with truncated variants forming...
Abstract The precise molecular architecture of synaptic active zones (AZs) gives rise to different structural and functional AZ states that fundamentally shape chemical neurotransmission. However, elucidating the nanoscopic protein arrangement at AZs is impeded by diffraction-limited resolution conventional light microscopy. Here we introduce new approaches quantify endogenous organization single-molecule in situ with super-resolution imaging direct stochastic optical reconstruction...
Significance Controlling neuronal activity in live tissue is a long sought-after goal the neurosciences. Channelrhodopsin-2 (ChR2) microbial-type rhodopsin that can be genetically expressed to depolarize neurons with light. Thereby, this “optogenetic tool” delivers cellular specificity and elegant options for studying basis of behavior intact organisms. Unfortunately, low-light transmission through pigmented greatly complicates light delivery target cells curtails experiments freely moving...
Three ionotropic glutamate receptor subunits, designated GluRIIA, GluRIIB, and GluRIII, have been identified at neuromuscular junctions of Drosophila . Whereas GluRIIA GluRIIB are redundant for viability, it was shown recently that GluRIII is essential both the synaptic localization viability Here we identify a fourth fifth subunit expressed in system, which name GluRIID GluRIIE. Both new subunits show to be necessary survival. Moreover, GluRIIE required expression all other subunits. All...
G-protein-coupled receptors (GPCRs) are typically regarded as chemosensors that control cellular states in response to soluble extracellular cues.However, the modality of stimuli recognized through adhesion GPCR (aGPCR), second largest class superfamily, is unresolved.Our study characterizes Drosophila aGPCR Latrophilin/ dCirl, a prototype member this enigmatic receptor class.We show dCirl shapes perception tactile, proprioceptive, and auditory chordotonal neurons, principal mechanosensors...
Adhesion-type G protein-coupled receptors (aGPCRs), a large molecule family with over 30 members in humans, operate organ development, brain function and govern immunological responses. Correspondingly, this receptor is linked to multitude of diverse human diseases. aGPCRs have been suggested possess mechanosensory properties, though their mechanism action fully unknown. Here we show that the Drosophila aGPCR Latrophilin/dCIRL acts neurons by modulating ionotropic currents, initiating step...
At presynaptic active zones (AZs), the frequently observed tethering of synaptic vesicles to an electron-dense cytomatrix represents a process largely unknown functional significance. Here, we identified hypomorphic allele, brp nude , lacking merely last 1% C-terminal amino acids (17 1740) zone protein Bruchpilot. In bodies were properly shaped, though entirely bare vesicles. While basal glutamate release was unchanged, paired-pulse and sustained stimulation provoked depression. Furthermore,...
The second messenger cyclic AMP (cAMP) plays an important role in synaptic plasticity. Although there is evidence for local control of transmission and plasticity, it less clear whether a similar spatial confinement cAMP signaling exists. Here, we suggest possible biophysical basis the site-specific regulation plasticity by cAMP, highly diffusible small molecule that transforms physiology synapses specific manner. By exploiting octopaminergic system Drosophila, which mediates structural via...
Neurotransmitter release is stabilized by homeostatic plasticity. Presynaptic potentiation (PHP) operates on timescales ranging from minute- to life-long adaptations and likely involves reorganization of presynaptic active zones (AZs). At Drosophila melanogaster neuromuscular junctions, earlier work ascribed AZ enlargement incorporating more Bruchpilot (Brp) scaffold protein a role in PHP. We use localization microscopy (direct stochastic optical reconstruction [dSTORM]) hierarchical...
DURING SHORT BURSTS OF NEURONAL ACTIVITY, CHANGES IN THE EFFICACY NEUROTRANSMITTER RELEASE ARE GOVERNED PRIMARILY BY TWO COUNTERACTING PROCESSES: (1) Ca(2+)-dependent elevations of vesicle release probability and (2) depletion synaptic vesicles. The dynamic interplay both processes contributes to the expression activity-dependent plasticity. Here, we exploited various facets short-term plasticity at Drosophila neuromuscular junction dissect these two processes. This enabled us rigorously...
Optogenetic manipulation of cells or living organisms became widely used in neuroscience following the introduction light-gated ion channel channelrhodopsin-2 (ChR2). ChR2 is a non-selective cation channel, ideally suited to depolarize and evoke action potentials neurons. However, its calcium (Ca2+) permeability single conductance are low for some applications longer-lasting increases intracellular might be desirable. Moreover, there need an efficient potassium (K+) that can rapidly inhibit...
Neurotransmitter is released from synaptic vesicles at the highly specialized presynaptic active zone (AZ). The complex molecular architecture of AZs mediates speed, precision and plasticity transmission. Importantly, structural functional properties vary significantly, even for a given connection. Thus, there appear to be distinct AZ states, which fundamentally influence neuronal communication by controlling positioning release vesicles. Vice versa, recent evidence has revealed that vesicle...
G protein-coupled receptors (GPCRs) comprise an expanded superfamily of in the human genome. Adhesion class (adhesion-GPCRs) form second largest GPCRs. Despite abundance, size, molecular structure, and functions facilitating cell matrix contacts a variety organ systems, adhesion-GPCRs are by far most poorly understood GPCR class. Adhesion-GPCRs possess unique with extended N-termini containing various adhesion domains. In addition, many autoproteolytically cleaved into N-terminal fragment...
The active zone (AZ) protein Bruchpilot (Brp) is essential for rapid glutamate release at Drosophila melanogaster neuromuscular junctions (NMJs). Quantal time course and measurements of action potential-waveform suggest that presynaptic fusion mechanisms are altered in brp null mutants (brp69). This could account their increased evoked excitatory postsynaptic current (EPSC) delay rise (by about one millisecond). To test the mechanism protraction brp69 AZs, we performed knock-down...
Pre- and postsynaptic forms of long-term potentiation (LTP) are candidate synaptic mechanisms underlying learning memory. At layer 5 pyramidal neurons, LTP increases the initial strength but also short-term depression during high-frequency transmission. This classical form presynaptic has been referred to as redistribution efficacy. However, remain unclear. We therefore performed whole-cell recordings from neurons in acute cortical slices rats analyzed function before after induction by...
Synapses can undergo rapid changes in size as well their vesicle release function during both plasticity processes and development. This fundamental property of neuronal cells requires the coordinated rearrangement synaptic membranes associated cytoskeleton, yet remarkably little is known how this coupling achieved. In a GFP exon-trap screen, we identified Drosophila melanogaster Basigin (Bsg) an immunoglobulin domain-containing transmembrane protein accumulating at periactive zones...
Synaptic plasticity shapes the development of functional neural circuits and provides a basis for cellular models learning memory. Hebbian describes an activity-dependent change in synaptic strength that is input-specific depends on correlated pre- postsynaptic activity. Although it recognized activity synapse are intimately linked, our mechanistic understanding coupling far from complete. Using Channelrhodopsin-2 to evoke vivo, we investigated at glutamatergic Drosophila neuromuscular...