A5007022136- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Photoreceptor and optogenetics research
- Neural dynamics and brain function
- Neuroscience and Neural Engineering
- Lipid Membrane Structure and Behavior
- Ion channel regulation and function
- Autoimmune Neurological Disorders and Treatments
- Neurobiology and Insect Physiology Research
- Retinal Development and Disorders
- Hearing, Cochlea, Tinnitus, Genetics
- Neuroinflammation and Neurodegeneration Mechanisms
- Vestibular and auditory disorders
- Peripheral Neuropathies and Disorders
- Neurogenesis and neuroplasticity mechanisms
- Nicotinic Acetylcholine Receptors Study
- Advanced Fluorescence Microscopy Techniques
- Genetics and Neurodevelopmental Disorders
- Receptor Mechanisms and Signaling
- Neurological disorders and treatments
- Neurogenetic and Muscular Disorders Research
- T-cell and B-cell Immunology
- Advanced Electron Microscopy Techniques and Applications
- Diet and metabolism studies
- Biochemical and Structural Characterization
Leipzig University
2015-2024
Jena University Hospital
2023-2024
University of Würzburg
2007-2024
Institute of Science and Technology Austria
2024
Czech Academy of Sciences, Institute of Physiology
2023-2024
University of Oxford
2023
Oxford University Hospitals NHS Trust
2023
European Neuroscience Institute Göttingen
2012-2014
Universitätsmedizin Göttingen
2013-2014
Australian National University
2006
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...
Information flow in neurons proceeds by integrating inputs dendrites, generating action potentials near the soma, and releasing neurotransmitters from nerve terminals axon. We found that striatum, acetylcholine-releasing induce potential firing distal dopamine axons. Spontaneous activity of cholinergic produced release extended beyond acetylcholine-signaling domains, traveling were readily recorded axons response to activation. In freely moving mice, acetylcholine covaried with movement...
The hyperpolarization-activated cation current ( I h ) plays an important role in regulating neuronal excitability, yet its native single-channel properties the brain are essentially unknown. Here we use variance-mean analysis to study of single channels apical dendrites cortical layer 5 pyramidal neurons vitro . In these neurons, find that have average unitary conductance 680 ± 30 fS n = 18). Spectral simulated and showed there is little or no channel flicker below kHz. contrast uniformly...
Sustained rate-coded signals encode many types of sensory modalities. Some synapses possess specialized ribbon structures, which tether vesicles, to enable high-frequency signaling. However, central lack these yet some can maintain signaling over a wide bandwidth. To analyze the underlying molecular mechanisms, we investigated function active zone core component Bassoon in cerebellar mossy fiber granule cell synapses. We show that short-term synaptic depression is enhanced knockout mice...
To probe exocytosis at a cortical glutamatergic synapse, we made capacitance measurements in whole-cell recorded hippocampal mossy fiber terminals. Evaluation of different methods by using morphology-based equivalent electrical model revealed that quantitative are possible this presynaptic structure. Voltage pulses leading to Ca 2+ inflow evoked large signals showed saturation with increasing pulse duration. The mean peak increase was 100 fF, corresponding pool ≈1,400 releasable vesicles....
How can synapses change the amount of neurotransmitter released during synaptic plasticity? Although release in general is intensely investigated, its determinants plasticity are still poorly understood. As a model for plastic strengthening release, we here use well-established presynaptic homeostatic compensation interference with postsynaptic glutamate receptors at Drosophila neuromuscular junction. Combining short-term analysis, cumulative EPSC fluctuation and quantal modeling, found an...
Synaptic inhibition is a central factor in the fine tuning of neuronal activity nervous system. Symptoms consistent with reduced such as stiffness, spasms and anxiety occur paraneoplastic stiff person syndrome autoantibodies against intracellular synaptic protein amphiphysin. Here we show that intrathecal application purified anti-amphiphysin immunoglobulin G antibodies induces syndrome-like symptoms rats, including stiffness muscle spasms. Using vivo recordings Hoffmann reflexes dorsal root...
Neurons relay information via specialized presynaptic compartments for neurotransmission. Unlike conventional organelles, the apparatus characterizing neuronal presynapse must form de novo. How components neurotransmission are transported and assembled is poorly understood. Our results show that rare late endosomal signaling lipid phosphatidylinositol 3,5-bisphosphate [PI(3,5)P
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,...
Presynaptic action potential spikes control neurotransmitter release and thus interneuronal communication. However, the properties dynamics of presynaptic in neocortex remain enigmatic because boutons are small direct patch-clamp recordings have not been performed. Here, we report from neocortical pyramidal neurons interneurons. Our data reveal rapid large potentials layer 5 fast-spiking interneurons reliably propagating into axon collaterals. For in-depth analyses, establish mature cultured...
The Ca 2+ -dependence of the priming, fusion, and replenishment synaptic vesicles are fundamental parameters controlling neurotransmitter release plasticity. Despite intense efforts, these important steps in vesicles’ cycle remain poorly understood due to technical challenge disentangling vesicle replenishment. Here, we investigated -sensitivity at mossy fiber synapses rodent cerebellum, which characterized by fast mediating high-frequency signaling. We found that basal free concentration...
Anti-NMDA receptor autoantibodies (NMDAR-Abs) in patients with NMDAR encephalitis cause severe disease symptoms resembling psychosis and cognitive dysfunction. After passive transfer of patients' cerebrospinal fluid or human monoclonal anti-GluN1-autoantibodies mice, we find a disrupted excitatory-inhibitory balance resulting from CA1 neuronal hypoexcitability, reduced AMPA (AMPAR) signaling, faster synaptic inhibition acute hippocampal slices. Functional alterations are also reflected...
Abstract One striking clinical hallmark in patients with autoantibodies to leucine-rich glioma inactivated 1 (LGI1) is the very frequent focal seizure semiologies, including faciobrachial dystonic seizures (FBDS), addition amnesia. Polyclonal serum IgGs have successfully modelled cognitive changes vivo but not seizures. Hence, it remains unclear whether LGI1-autoantibodies are sufficient cause We tested this molecularly precise monoclonal antibodies directed against LGI1 [LGI1-monoclonal...
Cytotoxic CD8 + T cells are considered important effector contributing to neuronal damage in inflammatory and degenerative CNS disorders. Using time-lapse video microscopy two-photon imaging combination with whole-cell patch-clamp recordings, we here show that major histocompatibility class I (MHC I)-restricted antigen presentation cell receptor specificity determine T-cell locomotion culture hippocampal brain slices. Two separate functional consequences result from a direct cell–cell...
Paired-pulse facilitation (PPF) is a dynamic enhancement of transmitter release considered crucial in CNS information processing. The mechanisms PPF remain controversial and may differ between synapses. Endogenous Ca(2+) buffers such as parvalbumin (PV) calbindin-D28k (CB) are regarded important modulators PPF, with PV acting an anti-facilitating buffer while saturation CB can promote PPF. We analysed at intracortical, recurrent Purkinje neuron (PN) to PN synapses, which show during...
Significance Calcium influx during action potentials triggers neurotransmitter release at presynaptic active zones. buffers limit the spread of calcium and restrict to vicinity channels. To sustain synchronous repetitive activity, rapid removal from zone is essential, but underlying mechanisms are unclear. Therefore, we focused on cerebellar mossy fiber synapses, which among fastest synapses in mammalian brain found very weak buffering. One might assume that strong buffering has potential...