Robust criticality in hair bundles

Weill Medical Coll Of Cornell Univ, New York NY

Investigators

Linked publications & trials

Abstract

PROJECT SUMMARY One in eight Americans aged twelve years and older?roughly 30 million people?suffers some degree of hearing loss. Hearing loss is broadly characterized as conductive, sensorineural, or mixed. The second of these categories encompasses the majority of people with hearing impairment and most frequently results from damage to hair cells, the cells in our ears responsible for detecting sound waves. Addressing this significant public-health concern requires a thorough understanding of the healthy operation of the hair cell and its signal- detection apparatus, the hair bundle. Our sense of hearing boasts exquisite sensitivity, precise frequency discrimination, and a broad dynamic range. A dynamic instability known as a Hopf bifurcation is thought to underlie these impressive features. Systems that exhibit a bifurcation demonstrate a qualitative change in behavior when a parameter of the system reaches its critical value. In hair bundles, this parameter might be calcium concentration or the external load applied to the bundle. Crossing a Hopf bifurcation incites spontaneous oscillations in a previously quiescent system. Just before this transition, when the system is on the verge of oscillating, small-amplitude stimuli are greatly enhanced. Analogously to a public address system turned up to the point of instability, our hearing derives its impressive features from this phenomenon. However, this enhanced response can occur for only the narrow range of parameter values that poise the system near the bifurcation. As a result, minuscule changes in certain parameters can compromise a hair bundle?s ability to detect sound. This poses a challenge to biological systems: How can hair cells exert tight control over parameters to ensure operation in close proximity to the bifurcation? This study seeks to answer this question from a novel perspective. Rather than achieving precise control over parameters, hair cells may employ a mechanism that broadens the region of influence of the dynamical instability. By widening the range of parameter values over which it can attain the desired level of performance, such a mechanism would render signal detection by a hair cell more robust. Evaluation of this hypothesis will be undertaken by first developing mathematical models of hair cell dynamics endowed with the proposed mechanism. Validation of these models will then be sought experimentally by delivering a variety of mechanical stimuli to hair bundles. These experiments will provide a means both to interrogate hair bundles for specific behaviors predicted by the model, and to identify potential effectors of the proposed mechanism. In addition to furthering our insight into how hair cells robustly detect signals, this work will deepen our understanding of the mechanisms responsible for the loss of auditory acuity that we experience following exposure to excessively loud sounds.