A5030613973- Hearing, Cochlea, Tinnitus, Genetics
- Photoreceptor and optogenetics research
- Cellular transport and secretion
- Hearing Loss and Rehabilitation
- Acoustic Wave Phenomena Research
- Ion channel regulation and function
- Lipid Membrane Structure and Behavior
- Retinal Development and Disorders
- Biochemical Analysis and Sensing Techniques
- RNA regulation and disease
- Neural dynamics and brain function
- Advanced Fluorescence Microscopy Techniques
- Neurobiology and Insect Physiology Research
- Bat Biology and Ecology Studies
- Cosmology and Gravitation Theories
- Axon Guidance and Neuronal Signaling
- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Calcium signaling and nucleotide metabolism
- Neuroscience and Neural Engineering
- Ion Channels and Receptors
- Vestibular and auditory disorders
- Immunodeficiency and Autoimmune Disorders
- Advanced Electron Microscopy Techniques and Applications
- Electron and X-Ray Spectroscopy Techniques
University of Göttingen
2012-2023
Universitätsmedizin Göttingen
2014-2023
Max Planck Institute for Multidisciplinary Sciences
2022-2023
Max Planck Institute for Biophysical Chemistry
2015-2021
Max Planck Institute of Experimental Medicine
2017-2021
University of Bern
2020
Bernstein Center for Computational Neuroscience Göttingen
2007-2014
Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103
2009
University of Würzburg
2007
Currently available cochlear implants are based on electrical stimulation of the spiral ganglion neurons. Optical with arrays micro-sized light-emitting diodes (µLEDs) promises to increase number distinguishable frequencies. Here, development a flexible GaN-based micro-LED array as an optical implant is reported for application in mouse model. The fabrication 15 µm thin and highly devices enabled by laser-based layer transfer process GaN-LEDs from sapphire polyimide-on-silicon carrier wafer....
We studied the role of synaptic ribbon for sound encoding at synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in mice lacking RIBEYE (RBEKO/KO). Electron immunofluorescence microscopy revealed a lack ribbons an assembly several small active zones (AZs) each contact. Spontaneous sound-evoked firing rates SGNs their compound action potential were reduced, indicating impaired transmission ribbonless IHC-SGN synapses. The temporal precision was recovery SGN-firing from...
Cochlear inner hair cells (IHCs) use Ca(2+)-dependent exocytosis of glutamate to signal sound information. Otoferlin (Otof), a C(2) domain protein essential for IHC and hearing, may serve as Ca(2+) sensor in vesicle fusion IHCs that seem lack the classical neuronal sensors synaptotagmin 1 (Syt1) Syt2. Support hypothesis otoferlin function comes from biochemical experiments, but additional roles late upstream have been indicated by physiological studies. Here, we tested functional equivalence...
Ca2+ influx triggers the release of synaptic vesicles at presynaptic active zone (AZ). A quantitative characterization signaling is critical for understanding transmission. However, this has remained challenging to establish required resolution. Here, we employ confocal and stimulated emission depletion (STED) microscopy quantify number (20-330) arrangement (mostly linear 70 nm × 100-600 clusters) channels AZs mouse cochlear inner hair cells (IHCs). Establishing STED imaging, analyze signals...
Ribbon synapses of cochlear inner hair cells (IHCs) employ efficient vesicle replenishment to indefatigably encode sound. In neurons, neuroendocrine and immune cells, depends on proteins the mammalian uncoordinated 13 (Munc13) Ca2+-dependent activator for secretion (CAPS) families, which prime vesicles exocytosis. Here, we tested whether Munc13 CAPS also regulate exocytosis in mouse IHCs by combining immunohistochemistry with auditory systems physiology IHC patch-clamp recordings mice...
Recent studies reveal great diversity in the structure, function, and efferent innervation of afferent synaptic connections between cochlear inner hair cells (IHCs) spiral ganglion neurons (SGNs), which likely enables audition to process a wide range sound pressures. By performing an extensive electron microscopic (EM) reconstruction neural circuitry mature mouse organ Corti, we demonstrate that SGN dendrites differ abundance composition manner dependent on their connectivity with IHCs. SGNs...
Abstract Ants rely heavily on olfaction for communication and orientation. Here we provide the first detailed structure–function analyses within an ant's central olfactory system asking whether in carpenter ant, Camponotus floridanus , pathway exhibits adaptations to processing many pheromonal general odors. Using fluorescent tracing, confocal microscopy, 3D‐analyses demonstrate that antennal lobe (AL) contains up ≈460 glomeruli organized seven distinct clusters innervated via sensory...
Sound coding at the auditory inner hair cell synapse requires graded changes in neurotransmitter release, triggered by sustained activation of presynaptic Ca(v)1.3 voltage-gated Ca(2+) channels. Central to their role this regard, channels cells show little Ca(2+)-dependent inactivation, a fast negative feedback regulation incoming ions, which depends on calmodulin association with channel alpha(1) subunit. inactivation characterizes nearly all including other excitable cells. The mechanism...
Cells assemble macromolecular complexes into scaffoldings that serve as substrates for catalytic processes. Years of molecular neurobiology research indicate neurotransmission depends on such optimization strategies. However, the topography presynaptic active zone (AZ), where transmitter is released upon synaptic vesicle (SV) fusion, remains to be visualized. Therefore, we implemented MINFLUX optical nanoscopy resolve AZ rod photoreceptors. This was facilitated by a novel sample...
Hearing relies on Ca 2+ influx-triggered exocytosis in cochlear inner hair cells (IHCs). Here we studied the role of channel subunit V β 2 hearing. Of 1–4 mRNAs, IHCs predominantly contained . was severely impaired mice lacking extracardiac tissues ( −/− ). This involved deficits amplification and sound encoding. Otoacoustic emissions were reduced or absent mice, which showed strongly elevated auditory thresholds single neuron recordings brainstem response measurements. greatly (by 68%)....
Synaptic vesicle recycling sustains high rates of neurotransmission at the ribbon-type active zones (AZs) mouse auditory inner hair cells (IHCs), but its modes and molecular regulation are poorly understood. Electron microscopy indicated presence clathrin-mediated endocytosis (CME) bulk endocytosis. The endocytic proteins dynamin, clathrin, amphiphysin expressed broadly distributed in IHCs. We used confocal vglut1-pHluorin imaging membrane capacitance (Cm) measurements to study spatial...
Ribbon synapses of cochlear inner hair cells (IHCs) are specialized to indefatigably transmit sound information at high rates. To understand the underlying mechanisms, structure-function analysis active zone (AZ) these is essential. Previous electron microscopy studies synaptic vesicle (SV) dynamics IHC AZ used potassium stimulation, which limited temporal resolution minutes. Here, we established optogenetic stimulation followed by quick freezing within milliseconds and tomography study...
Mutation in the clarin-1 gene (<i>Clrn1</i>) results loss of hearing and vision humans (Usher syndrome III), but role sensory hair cells is unknown. Clarin-1 predicted to be a four transmembrane domain protein similar members tetraspanin family. Mice carrying null mutation (<i>Clrn1</i><sup>−/−</sup>) show cell function possible defect ribbon synapse. We investigated using various <i>in vitro</i> vivo</i> approaches. by immunohistochemistry patch-clamp recordings Ca<sup>2+</sup> currents...
Rationale: Recently, abundant axial tubule (AT) membrane structures were identified deep inside atrial myocytes (AMs). Upon excitation, ATs rapidly activate intracellular Ca2+ release and sarcomeric contraction through extensive AT junctions, a cell-specific mechanism. While junctions with the sarcoplasmic reticulum contain unusually large clusters of ryanodine receptor 2 (RyR2) channels in mouse AMs, it remains unclear if similar protein networks exist across species, particularly those...
Proper connectivity between type I spiral ganglion neurons (SGNs) and inner hair cells (IHCs) in the cochlea is necessary for conveying sound information to brain mammals. Previous studies have shown that SGNs are heterogeneous form, function synaptic location on IHCs, but factors controlling their patterns of not well understood.
Auditory synaptopathy/neuropathy (AS/AN) is a distinct type of sensorineural hearing loss in which the cochlear sensitivity to sound (i.e. active amplification by outer hair cells) preserved whereas encoding inner cells and/or auditory nerve fibers disrupted owing genetic or environmental factors. Autosomal-dominant neuropathy 2 (AUNA2) was linked either chromosomal bands 12q24 13q34 large German family 2017. By whole-genome sequencing, we now detected 5500 bp deletion ATP11A on chromosome...