A5057549975- Hearing, Cochlea, Tinnitus, Genetics
- Hearing Loss and Rehabilitation
- Vestibular and auditory disorders
- Marine animal studies overview
- Neural dynamics and brain function
- Animal Vocal Communication and Behavior
- Ion channel regulation and function
- Axon Guidance and Neuronal Signaling
- Zebrafish Biomedical Research Applications
- Acoustic Wave Phenomena Research
- RNA Research and Splicing
- Connexins and lens biology
- Mechanical and Optical Resonators
- Developmental Biology and Gene Regulation
- Cellular Mechanics and Interactions
- Erythrocyte Function and Pathophysiology
- Bat Biology and Ecology Studies
- Microfluidic and Bio-sensing Technologies
- Plant and Biological Electrophysiology Studies
- Cancer-related molecular mechanisms research
- Biochemical Analysis and Sensing Techniques
- Muscle Physiology and Disorders
- Neuroscience and Neuropharmacology Research
- Hippo pathway signaling and YAP/TAZ
- Neurobiology and Insect Physiology Research
Howard Hughes Medical Institute
2016-2025
Rockefeller University
2015-2024
Chan Zuckerberg Initiative (United States)
2023
Tri-Institutional PhD Program in Chemical Biology
2023
Brigham and Women's Hospital
2023
University of Washington
2023
Seattle University
2023
Heidelberg University
2023
The Abdus Salam International Centre for Theoretical Physics (ICTP)
2020
Institut Curie
2001-2015
Hair cells, the primary receptors of auditory, vestibular, and lateral-line sensory systems, produce electrical signals in response to mechanical stimulation their apical hair bundles. We employed an vitro preparation intracellular recording investigate transduction mechanism cells sacculus from inner ear bullfrog (Rana catesbeiana). When stimulated directly by deflection bundles, these gave graded responses up 15 mV amplitude; peak sensitivity was about 20 mV/micron deflection. The...
Mechanoelectrical transduction by hair cells of the frog's internal ear displays adaptation: electrical response to a maintained deflection bundle declines over period tens milliseconds. We investigated role mechanics in adaptation measuring changes hair-bundle stiffness following application force stimuli. Following step stimulation with glass fiber, saccular cell initially had approximately equal 1 mN X m-1. The then declined steady-state level near 0.6 m-1 time course comparable that...
Our hearing organ, the cochlea, evidently poises itself at a Hopf bifurcation to maximize tuning and amplification. We show that in this condition several effects are expected be generic: compression of dynamic range, infinitely sharp zero input, generation combination tones. These ``essentially'' nonlinear they become more marked smaller forcing: there is no audible sound soft enough not evoke them. All well-documented aspects therefore appear consequences same underlying mechanism.
A crucial event in the hearing process is transduction of mechanical stimuli into electrical signals by hair cells, sensory receptors internal ear. Stimulation results rapid opening ionic channels mechanically sensitive organelles these their bundles. These channels, which are nonselectively permeable, directly excited hair-bundle displacement. Hair cells selectively responsive to particular frequencies stimulation, both due properties bundles and because an ensemble that constitute resonator.
The vertebrate hair cell is a sensory receptor that responds to mechanical stimulation of its bundle, which usually consists numerous large microvilli (stereocilia) and single true cilium (the kinocilium). We have examined the roles these two components bundle by recording intracellularly from bullfrog saccular cells. Detachment kinocilium deflection this produces no potentials. Mechanical stereocilia, however, elicits responses normal amplitude sensitivity. Scanning electron microscopy...
Abstract Hippo signaling is an evolutionarily conserved pathway that restricts growth and regeneration predominantly by suppressing the activity of transcriptional coactivator Yap. Using a high-throughput phenotypic screen, we identified potent non-toxic activator In vitro kinase assays show compound acts as ATP-competitive inhibitor Lats kinases—the core enzymes in signaling. The substance prevents Yap phosphorylation induces proliferation supporting cells murine inner ear, cardiomyocytes,...
To enhance their mechanical sensitivity and frequency selectivity, hair cells amplify the stimuli to which they respond. Although cell-body contractions of outer are thought mediate active process in mammalian cochlea, vertebrates without display highly sensitive, sharply tuned hearing spontaneous otoacoustic emissions. In these animals amplifier must reside elsewhere. We report physiological evidence that amplification can stem from movement bundle, cell’s mechanosensitive organelle....
1. By the use of whole‐cell and excised‐patch tight‐seal recording techniques, we studied ionic conductances in voltage‐clamped solitary hair cells isolated from bull‐frog's sacculus. As a basis for assessing their contributions to cell electrical resonance, developed kinetic models describing voltage‐dependent Ca2+ Ca2+‐dependent K+ conductances. 2. A transient current (IA) was activated by steps potentials positive ‐50 mV holding more negative than ‐70 mV. In steady state, fully...
As in other excitable cells, the ion channels of sensory receptors produce electrical signals that constitute cellular response to stimulation. In photoreceptors, olfactory neurons, and some gustatory receptors, these essentially report results antecedent events a cascade chemical reactions. The mechanoelectrical transduction hair by contrast, are coupled directly stimulus. consequence, mechanical properties shape our hearing process from outset transduction. Channel gating introduces...
One prominent manifestation of mechanical activity in hair cells is spontaneous otoacoustic emission, the unprovoked emanation sound by an internal ear. Because active bundle motility probably constitutes process nonmammalian cells, we investigated ability bundles bullfrog's sacculus to produce oscillations that might underlie emissions. When maintained normal ionic milieu ear, many oscillated spontaneously through distances as great 80 nm at frequencies 5–50 Hz. Whole-cell recording...
Hearing and balance rely on the ability of hair cells in inner ear to sense miniscule mechanical stimuli. In each cell, sound or acceleration deflects mechanosensitive bundle, a tuft rigid stereocilia protruding from cell's apical surface. By altering tension gating springs linked mechanically sensitive transduction channels, this deflection changes channels' open probability elicits an electrical response. To detect weak stimuli despite energy losses caused by viscous dissipation, cell can...