Publications

Assistant Professor of Otolaryngology - Head & Neck Surgery (OHNS)

Publications

Coupling between the stereocilia of rat sensory inner-hair-cell hair bundles is weak, shaping their sensitivity to stimulation. The Journal of neuroscience : the official journal of the Society for Neuroscience Scharr, A. L., Maoileidigh, D. O., Ricci, A. J. 2023 More

Abstract

The hair bundle is the universal mechanosensory organelle of auditory, vestibular, and lateral-line systems. A bundle comprises mechanically coupled stereocilia, whose displacements in response to stimulation activate a receptor current. The similarity of stereociliary displacements within a bundle regulates fundamental properties of the receptor current like its speed, magnitude, and sensitivity. However, the dynamics of individual stereocilia from the mammalian cochlea in response to a known bundle stimulus has not been quantified. We developed a novel high-speed system, which dynamically stimulates and tracks individual inner-hair-cell stereocilia from male and female rats. Stimulating 2-3 of the tallest stereocilia within a bundle (nonuniform stimulation) caused dissimilar stereociliary displacements. Stereocilia further from the stimulator moved less, but with little delay, implying that there is little slack in the system. Along the axis of mechanical sensitivity, stereocilium displacements peaked and reversed direction in response to a step stimulus. A viscoelastic model explained the observed displacement dynamics, which implies that coupling between the tallest stereocilia is effectively viscoelastic. Coupling elements between the tallest inner-hair-cell stereocilia were 2-3 times stronger than elements anchoring stereocilia to the cell's surface but were 10-10,000 times weaker than those of a well-studied non-cochlear hair bundle. Coupling was too weak to ensure that stereocilia move similarly in response to nonuniform stimulation at auditory frequencies. Our results imply that more uniform stimulation across the tallest stereocilia of an inner-hair-cell bundle in vivo is required to ensure stereociliary displacement similarity, increasing the speed, sensitivity, and magnitude of the receptor current.SIGNIFICANCE STATEMENT:Generation of the hair cell's receptor current is the first step in electrically encoding auditory information in the hearing organs of all vertebrates. The receptor current is shaped by mechanical coupling between stereocilia in each hair cell's hair bundle. Here we provide foundational information on the mechanical coupling between stereocilia of cochlear inner hair cells. In contrast to other types of hair cell, coupling between inner hair cell stereocilia is weak, causing slower, smaller, and less sensitive receptor currents in response to stimulation of few, rather than many, stereocilia. Our results imply that inner hair cells need many stereocilia to be stimulated in vivo to ensure fast, large, and sensitive receptor currents.

View details for DOI 10.1523/JNEUROSCI.1588-22.2023

View details for PubMedID 36746628
Dimensions of a Living Cochlear Hair Bundle Front Cell Dev Biol Miller, K. K., Atkinson, P., Mendoza, K., Ó Maoiléidigh, D., Grillet, N. 2021; 9: 742529 More

Abstract

The hair bundle is the mechanosensory organelle of hair cells that detects mechanical stimuli caused by sounds, head motions, and fluid flows. Each hair bundle is an assembly of cellular-protrusions called stereocilia, which differ in height to form a staircase. Stereocilia have different heights, widths, and separations in different species, sensory organs, positions within an organ, hair-cell types, and even within a single hair bundle. The dimensions of the stereociliary assembly dictate how the hair bundle responds to stimuli. These hair-bundle properties have been measured previously only to a limited degree. In particular, mammalian data are either incomplete, lack control for age or position within an organ, or have artifacts owing to fixation or dehydration. Here, we provide a complete set of measurements for postnatal day (P) 11 C57BL/6J mouse apical inner hair cells (IHCs) obtained from living tissue, tissue mildly-fixed for fluorescent imaging, or tissue strongly fixed and dehydrated for scanning electronic microscopy (SEM). We found that hair bundles mildly-fixed for fluorescence had the same dimensions as living hair bundles, whereas SEM-prepared hair bundles shrank uniformly in stereociliary heights, widths, and separations. By determining the shrinkage factors, we imputed live dimensions from SEM that were too small to observe optically. Accordingly, we created the first complete blueprint of a living IHC hair bundle. We show that SEM-prepared measurements strongly affect calculations of a bundle's mechanical properties - overestimating stereociliary deflection stiffness and underestimating the fluid coupling between stereocilia. The methods of measurement, the data, and the consequences we describe illustrate the high levels of accuracy and precision required to understand hair-bundle mechanotransduction.

View details for DOI 10.3389/fcell.2021.742529

View details for PubMedCentralID PMC8657763
Bilateral spontaneous otoacoustic emissions show coupling between active oscillators in the two ears Biophysical Journal Roongthumskul, Y., Ó Maoiléidigh, D., Hudspeth, A. 2019; 116: 2023-2034
A Bundle of Mechanisms: Inner-Ear Hair-Cell Mechanotransduction Trends in neurosciences Ó Maoiléidigh, D., Ricci, A. J. 2019; 42: 221-236
Multiple mechanisms for stochastic resonance are inherent to sinusoidally driven noisy Hopf oscillators. Physical Review E O Maoileidigh, D. 2018; 97: 022226 More

Abstract

To ensure their sensitivity to weak periodic signals, some physical systems likely operate near a Hopf bifurcation. Many systems operating near such a bifurcation exhibit stochastic resonance, but it is unclear which mechanisms for resonance are inherent to the bifurcation. To address this question, we study the sinusoidally forced dynamics of noisy supercritical and subcritical Hopf oscillators. We find four qualitatively different mechanisms for stochastic resonance and determine the conditions for each type of resonance.

View details for DOI 10.1103/PhysRevE.97.022226
Sinusoidal-signal detection by active, noisy oscillators on the brink of self-oscillation Physica D Ó Maoiléidigh, D., Hudspeth, A. J. 2018; 378-379: 33-45
Homeostatic enhancement of sensory transduction. Proceedings of the National Academy of Sciences of the United States of America Milewski, A. R., Ó Maoiléidigh, D., Salvi, J. D., Hudspeth, A. J. 2017; 114 (33): E6794-E6803 More

Abstract

Our sense of hearing boasts exquisite sensitivity, precise frequency discrimination, and a broad dynamic range. Experiments and modeling imply, however, that the auditory system achieves this performance for only a narrow range of parameter values. Small changes in these values could compromise hair cells' ability to detect stimuli. We propose that, rather than exerting tight control over parameters, the auditory system uses a homeostatic mechanism that increases the robustness of its operation to variation in parameter values. To slowly adjust the response to sinusoidal stimulation, the homeostatic mechanism feeds back a rectified version of the hair bundle's displacement to its adaptation process. When homeostasis is enforced, the range of parameter values for which the sensitivity, tuning sharpness, and dynamic range exceed specified thresholds can increase by more than an order of magnitude. Signatures in the hair cell's behavior provide a means to determine through experiment whether such a mechanism operates in the auditory system. Robustness of function through homeostasis may be ensured in any system through mechanisms similar to those that we describe here.

View details for DOI 10.1073/pnas.1706242114

View details for PubMedID 28760949
Mechanical Transduction Processes in the Hair Cell Understanding the Cochlea David, C. P., Ó Maoiléidigh, D., Ashmore, J. F. Springer International Publishing. 2017: 75–111
Identification of Bifurcations from Observations of Noisy Biological Oscillators. Biophysical journal Salvi, J. D., Ó Maoiléidigh, D., Hudspeth, A. J. 2016; 111 (4): 798-812 More

Abstract

Hair bundles are biological oscillators that actively transduce mechanical stimuli into electrical signals in the auditory, vestibular, and lateral-line systems of vertebrates. A bundle's function can be explained in part by its operation near a particular type of bifurcation, a qualitative change in behavior. By operating near different varieties of bifurcation, the bundle responds best to disparate classes of stimuli. We show how to determine the identity of and proximity to distinct bifurcations despite the presence of substantial environmental noise. Using an improved mechanical-load clamp to coerce a hair bundle to traverse different bifurcations, we find that a bundle operates within at least two functional regimes. When coupled to a high-stiffness load, a bundle functions near a supercritical Hopf bifurcation, in which case it responds best to sinusoidal stimuli such as those detected by an auditory organ. When the load stiffness is low, a bundle instead resides close to a subcritical Hopf bifurcation and achieves a graded frequency response-a continuous change in the rate, but not the amplitude, of spiking in response to changes in the offset force-a behavior that is useful in a vestibular organ. The mechanical load in vivo might therefore control a hair bundle's responsiveness for effective operation in a particular receptor organ. Our results provide direct experimental evidence for the existence of distinct bifurcations associated with a noisy biological oscillator, and demonstrate a general strategy for bifurcation analysis based on observations of any noisy system.

View details for DOI 10.1016/j.bpj.2016.07.027

View details for PubMedID 27558723

View details for PubMedCentralID PMC5002087
Control of a hair bundle's mechanosensory function by its mechanical load. Proceedings of the National Academy of Sciences of the United States of America Salvi, J. D., Ó Maoiléidigh, D., Fabella, B. A., Tobin, M., Hudspeth, A. J. 2015; 112 (9): E1000-9 More

Abstract

Hair cells, the sensory receptors of the internal ear, subserve different functions in various receptor organs: they detect oscillatory stimuli in the auditory system, but transduce constant and step stimuli in the vestibular and lateral-line systems. We show that a hair cell's function can be controlled experimentally by adjusting its mechanical load. By making bundles from a single organ operate as any of four distinct types of signal detector, we demonstrate that altering only a few key parameters can fundamentally change a sensory cell's role. The motions of a single hair bundle can resemble those of a bundle from the amphibian vestibular system, the reptilian auditory system, or the mammalian auditory system, demonstrating an essential similarity of bundles across species and receptor organs.

View details for DOI 10.1073/pnas.1501453112

View details for PubMedID 25691749

View details for PubMedCentralID PMC4352782