Biology subjects

Fridberger, A.

Publications and source records attributed to Fridberger, A..

4 recordsLinked to original sources

bioRxiv2026

A Newly Identified Role of the Tectorial Membrane in Aminoglycoside Ototoxicity

Aminoglycoside (AG) antibiotic safety is limited by ototoxicity, the mitigation of which is vital considering bacterial resistance mediated erosion of our antibiotic arsenal. Previously, we observed tectorial membrane (TM) sequestration of Ca2+. We hypothesized that the TM sequesters other cations, including the AG gentamicin. We proposed to test the effect of TM genetic ablation on ototoxicity and TM-AG sequestration. After intraperitoneal AG-furosemide, TM-lacking Tecta{Delta}ENT/{Delta}ENT mice showed limited outer hair cell loss, unlike wildtype littermates. Spectroscopy measurements of gentamicin-Texas red (GTTR) were made in isolated wildtype and TectaY1870C TMs and guinea pig cochleae following direct or intraperitoneal GTTR administration. TM-GTTR sequestration was observed in all cases, while negatively correlated with TectaY1870C zygosity. In summary, we discovered a novel TM component in the AG ototoxicity pathway. Intact TM structure is necessary for sequestration, and the TM modulates AG ototoxicity. TM-GTTR sequestration following systemic injection indicates that this phenomenon occurs during AG therapy. Single sentence summaryOtotoxic aminoglycosides collect inside the acellular tectorial membrane of the inner ear, likely due to electrostatic interactions, and the structural status of that membrane modulates the toxic effect of those aminoglycosides on sensory hair cells.

physiology↗

bioRxiv2025

Slow Mechanical Filtering by Outer Hair Cells Enhances Rather than Limits Receptor Potential Kinetics

The cochlea protects itself from intense sound via slow mechanical contractions, but the real-time kinetics linking this process to the stimulus-evoked electrical potentials have remained unresolved. Here, using high-speed confocal imaging with AI-driven analysis, we synchronously measured organ of Corti mechanics and stimulus-evoked potentials in the living isolated guinea pig cochlea. We discovered an inverse kinetic relationship: the outer hair cells (OHC) slow, somatic contraction is essential for generating a fast electrical response. Pharmacologically blocking the OHC motor protein prestin inverted this dynamic; the OHCs mechanical contraction became faster, while the normally rapid electrical potential became nearly ten times slower. These findings indicate that slow OHC motility is not merely a byproduct of overstimulation but a control mechanism. It functions to regulate and sharpen the kinetics of the stimulus-evoked potential, providing a cellular-level explanation for how the hearing organ protects itself while maintaining temporal fidelity during intense sound exposure.

neuroscience↗

bioRxiv2020

Radixin modulates stereocilia function and contributes to cochlear amplification

The stereocilia of the sensory cells in the inner ear contain high levels of the actin-binding protein radixin, encoded by the RDX gene. Radixin which is associated with mechanotransduction process such as PIP2 is known to be important for hearing but its functional role remains obscure. To determine how radixin influences hearing sensitivity, we used a custom rapid imaging technique to directly visualize stereocilia motion while measuring the amplitude of the electrical potentials produced by sensory cells during acoustic stimulation. Experiments were performed in guinea pigs, where upon blocking radixin, a large decrease in sound-evoked electrical potentials occurred. Despite this decrease other important functional measures, such as electrically induced sensory cell motility and the sound-evoked deflections of stereocilia, showed a minor amplitude increase. This unique set of functional properties alterations demonstrate that radixin is necessary to ensure that the inner ear converts sound into electrical signals at acoustic rates. Radixin is therefore a necessary and important component of the cochlear amplifier, the energy-consuming process that boosts hearing sensitivity by up to 60 dB.

neuroscience↗

bioRxiv2017

Static length changes of cochlear outer hair cells can tune low-frequency hearing

The cochlea not only transduces sound-induced vibration into neural spikes, it also amplifies weak sound to boost its detection. Actuators of this active process are sensory outer hair cells in the organ of Corti, whereas the inner hair cells transduce the resulting motion into electric signals that propagate via the auditory nerve to the brain. However, how the outer hair cells modulate the stimulus to the inner hair cells remains unclear. Here, we combine theoretical modeling and experimental measurements near the cochlear apex to study the way in which length changes of the outer hair cells deform the organ of Corti. We develop a geometry-based kinematic model of the apical organ of Corti that reproduces salient, yet counter-intuitive features of the organs motion. Our analysis further uncovers a mechanism by which a static length change of the outer hair cells can sensitively tune the signal transmitted to the sensory inner hair cells. When the outer hair cells are in an elongated state, stimulation of inner hair cells is largely inhibited, whereas outer hair cell contraction leads to a substantial enhancement of sound-evoked motion near the hair bundles. This novel mechanism for regulating the sensitivity of the hearing organ applies to the low frequencies that are most important for the perception of speech and music. We suggest that the proposed mechanism might underlie frequency discrimination at low auditory frequencies, as well as our ability to selectively attend auditory signals in noisy surroundings.\n\nAuthor summaryOuter hair cells are highly specialized force producers inside the inner ear: they can change length when stimulated electrically. However, how exactly this electromotile effect contributes to the astonishing sensitivity and frequency selectivity of the inner ear has remained unclear. Here we show for the first time that static length changes of outer hair cells can sensitively regulate how much of a sound signal is passed on to the inner hair cells that forward the signal to the brain. Our analysis holds for the apical region of the inner ear that is responsible for detecting the low frequencies that matter most in speech and music. This shows a mechanisms for how frequency-selectivity can be achieved at low frequencies. It also opens a path for the efferent neural system to regulate hearing sensitivity.

biophysics↗