A5021834441- Hearing, Cochlea, Tinnitus, Genetics
- Vestibular and auditory disorders
- Biochemical Analysis and Sensing Techniques
- Photoreceptor and optogenetics research
- Connexins and lens biology
- Erythrocyte Function and Pathophysiology
- Advanced Electron Microscopy Techniques and Applications
- RNA regulation and disease
- Hearing Loss and Rehabilitation
- Plant Molecular Biology Research
- Neural dynamics and brain function
- Acoustic Wave Phenomena Research
- Force Microscopy Techniques and Applications
- ATP Synthase and ATPases Research
- RNA modifications and cancer
- Cell Image Analysis Techniques
- Digital Holography and Microscopy
- Ion Channels and Receptors
- Structural Analysis and Optimization
- Advanced Materials and Mechanics
- Neurobiology and Insect Physiology Research
- Noise Effects and Management
- Electron and X-Ray Spectroscopy Techniques
- Mitochondrial Function and Pathology
- Machine Learning in Materials Science
University of Göttingen
2014-2025
Universitätsmedizin Göttingen
2014-2025
University Medical Center
2024
Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103
2022-2024
Multiscale Bioimaging
2022-2023
Synapse (Netherlands)
2022
Collaborative Research Group
2022
Synapse (Greece)
2017
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...
Ribbon synapses of cochlear inner hair cells (IHCs) undergo molecular assembly and extensive functional structural maturation before hearing onset. Here, we characterized the nanostructure IHC from late prenatal mouse embryo stages (embryonic days 14-18) into adulthood [postnatal day (P)48] using electron microscopy tomography as well optical nanoscopy apical turn organs Corti. We find that synaptic ribbon precursors arrive at presynaptic active zones (AZs) after afferent contacts have been...
EF-hand Ca(2+)-binding proteins are thought to shape the spatiotemporal properties of cellular Ca(2+) signaling and prominently expressed in sensory hair cells ear. Here, we combined genetic disruption parvalbumin-α, calbindin-D28k, calretinin mice with patch-clamp recording, vivo physiology, mathematical modeling study their role signaling, exocytosis, sound encoding at synapses inner (IHCs). IHCs lacking all three showed excessive exocytosis during prolonged depolarizations, despite...
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...
Mitochondrial oxidative phosphorylation (OXPHOS) fuels cellular ATP demands. OXPHOS defects lead to severe human disorders with unexplained tissue specific pathologies. gene expression is essential for biogenesis since core subunits of the complexes are mitochondrial-encoded. COX14 required translation COX1, central mitochondrial-encoded subunit complex IV. Here we describe a mutant mouse corresponding patient IV deficiency.
Our sense of hearing processes sound intensities spanning six orders magnitude. In the ear, postsynaptic spiral ganglion neurons (SGNs) tile this intensity range with their firing rate codes. Presynaptic inner hair cells (IHCs) vary Ca 2+ -influx among active zones (AZs) diversifying glutamate release and likely contributing to SGN diversity. Here we show that low-voltage activation IHC-Ca mice, modeling human V 1.3 A749G mutation, increases spontaneous SGN-firing lowers threshold. Altered...
Multi-scale X-ray phase contrast tomography (XPCT) enables three-dimensional (3D), non-destructive imaging of intact small animal cochlea and apical cochlear turns. Here we report on post-mortem excised non-human primate rodent cochleae at different [Formula: see text]-CT nano-CT synchrotron instruments. We explore sample embeddings, stainings regimes. Under optimized conditions preparation, instrumentation, protocol, retrieval, high image quality detail level can be achieved in 3D...
Abstract Inner hair cells (IHCs) are the primary receptors for hearing. They housed in cochlea and convey sound information to brain via synapses with auditory nerve. IHCs have been thought be electrically metabolically independent from each other. We report that, upon developmental maturation, mice 30% of electrochemically coupled ‘mini-syncytia’. This coupling permits transfer fluorescently-labeled metabolites macromolecular tracers. The membrane capacitance, Ca 2+ -current, resting...
Abstract Electron microscopy is an important technique for the study of synaptic morphology and its relation to function. The data analysis this task requires segmentation relevant structures, such as vesicles, active zones, mitochondria, presynaptic densities, ribbons, compartments. Previous studies were predominantly based on manual segmentation, which very time-consuming prevented systematic large datasets. Here, we introduce SynapseNet, a tool automatic synapses in electron micrographs....
In mammals, spatial orientation is synaptically-encoded by sensory hair cells of the vestibular labyrinth. Vestibular (VHCs) harbor synaptic ribbons at their presynaptic active zones (AZs), which play a critical role in molecular scaffolding and facilitate release vesicular replenishment. With advancing age, prevalence deficits increases; yet, underlying mechanisms are not well understood possible accompanying morphological changes VHC synapses have yet been systematically examined. We...
Abstract Inner hair cells (IHCs) are the primary receptors for hearing. They housed in cochlea and convey sound information to brain via synapses with auditory nerve. IHCs have been thought be electrically metabolically independent from each other. We report that, upon developmental maturation, 30% of electrochemically coupled ‘mini-syncytia’. This coupling permits transfer fluorescently-labeled metabolites macromolecular tracers. The membrane capacitance, Ca 2+ -current, resting current...
The peripheral auditory system in rodents reaches its functional maturity within the postnatal days 12 – 14. This maturation involves structural and remodeling of inner hair cell (IHC) presynaptic active zones (AZ). latter process is essentially required for exquisite temporal precision exceedingly high neurotransmission rates observed at this synapse fundamental synaptic sound encoding. To date, molecular characterization underlying these developmental processes remain poorly understood.
Das periphere auditorische System der Maus entwickelt seine Funktionsbereitschaft in den ersten 12 – 14 postnatalen Tagen. Dieser Reifungsprozess beinhaltet sowohl eine strukturelle als auch funktionelle Re-Modellierung präsynaptischen aktiven Zonen (AZ) von inneren Haarzellen (IHZ), welche für die zeitliche Präzision und hohen Transmitterfreisetzungsraten dieser Synapse somit Schallkodierung im Innenohr unerlässlich sind. Die molekulare Grundlage Verlauf Reifungsperiode verbleiben bislang...
Abstract 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...
Abstract Cochlear inner hair cells (IHCs) form specialized ribbon synapses with spiral ganglion neurons that tireless-ly transmit sound information at high rates over long time periods extreme temporal precision. This functional specialization is essential for precise encoding and attributed to a distinct molecular machinery unique players or splice variants compared conventional neuronal synapses. Among these the active zone (AZ) scaffold protein piccolo/aczonin, which represented by its...
Abstract In mammals, spatial orientation is synaptically-encoded by sensory hair cells of the vestibular labyrinth. Vestibular (VHCs) harbor synaptic ribbons at their presynaptic active zones (AZs), which play a critical role in molecular scaffolding and facilitate release vesicular replenishment. With advancing age, prevalence deficits increases; yet, direct link to functional decline VHC ribbon synapses remains be demonstrated. To address this issue, we investigated effects aging on...