The remarkable cochlear amplifier

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Abstract

This composite article is intended to give the experts in the field of cochlear mechanics an opportunity to voice their personal opinion on the one mechanism they believe dominates cochlear amplification in mammals. A collection of these ideas are presented here for the auditory community and others interested in the cochlear amplifier. Each expert has given their own personal view on the topic and at the end of their commentary they have suggested several experiments that would be required for the decisive mechanism underlying the cochlear amplifier. These experiments are presently lacking but if successfully performed would have an enormous impact on our understanding of the cochlear amplifier.

Introduction

by Barbara Canlon

Mechanoelectrical transduction in the mammalian cochlea occurs due to vibrations of the basilar membrane that cause the stereocilia of the outer hair cells to deflect resulting in the gating of mechanosensitive transducer channels. There is an active mechanical response that amplifies low-level and compresses high-level basilar membrane displacements. The amplification is frequency dependent and results in high auditory sensitivity and an extended dynamic range.

The idea of an active process in the cochlea was first proposed by Gold (1948), and has been the focus of intense research for more many decades. In 1983 Hallowell Davis wrote, “We are in the midst of a major breakthrough in auditory physiology. Recent experiments force us, I believe, to accept a revolutionary new hypothesis concerning the action of the cochlea namely, that an active process increases the vibration of the basilar membrane (BM) by energy provided somehow in the organ of Corti”. In his insightful paper he describes a cochlear model to include an active process and its underlying properties.

Numerous scientific reports have been aimed at characterizing the biophysical, biochemical and molecular properties of the active process. Two main mechanisms have been put forth to explain the mechanism underlying the cochlear amplifier. In brief, one is a voltage-dependent somatic motility resulting from the activity of the motor protein prestin in the lateral membrane of the outer hair cells. The other is dependent on hair-bundle motility driven by calcium currents. There is a continuum of articles being published regarding the role of stereocilia versus somatic motility as the mechanism for the active process and these publications often spark up intense discussions among the auditory community.

There are two main mechanisms discussed in these commentaries (somatic and stereocilia based active processes) and several authors are suggesting that mechanical amplification is driven by both somatic and stereocilia contributions. However, all authors are in agreement that further experimentation is needed to be fully convinced of the mechanistic basis of outer hair cell motility. There are still many basic questions that remain to be answered before the basis of the cochlear amplifier or amplifiers is fully understood. As mentioned in the commentaries, some basic experiments that are needed include determining the characteristics of amplification along the basilar membrane (high versus low frequencies); dissecting the contribution of somatic motility from hair-bundle motility via genetic modifications and finally targeted biophysical experiments to alter ion channels and protein levels in hair cell membranes and in stereocilia. Hopefully the suggested experiments will soon be tested by inquisitive scientists to help generate a full characterization of the cochlear amplifier. There is most probably no definitive experiment but a combination of studies that will help solved the many years of debate and controversy around the cochlear amplifier.

Section snippets

Cochlear amplification – Somatic or stereocilial forces? A first-person response

by Jonathan Ashmore

It is always said that experimental artefacts are the most convincing of results. From the moment that Brownell and colleagues in Geneva reported that when an outer hair cell was depolarised it shortened (Brownell et al., 1985), there was always a nagging doubt that this was an epiphenomenon – a consequence of doing the experiments in a particular way. The Geneva finding used Ake Flock’s earlier (re-)discovery at the Karolinska Institute of how to produce good-looking

Top connectors of the hair-bundle are required for waveform distortion and suppression masking but not cochlear amplification

by Paul Avan, Christine Petit*

Several major properties of sound perception rest upon the pre-processing of sound by the outer hair cells (OHC) in the mammalian inner ear, that is, one stage ahead of the mechanoelectrical transduction eventually achieved by inner hair cells (IHC). Those OHCs are the key element of a feedback loop whereby sound stimuli are mechanically amplified in a widely popular view (Davis, 1983, Gold, 1948). It is the most common explanation brought forward for explaining

Membrane-based amplification in hearing

by William E. Brownell*

Acoustic vibrations enter and neuronal action potentials leave the inner ear. An interplay of mechanical and electrical energy results in hair-cell receptor potentials that ultimately trigger neurotransmitter release at the afferent synapse. The diffusion of neurotransmitter across the synaptic cleft depolarizes 8th nerve terminals and initiates action potentials that travel to the central nervous system. The action potentials encode information about the spectral and

Feedback in the cochlea

by Peter Dallos

Science thrives on controversy and scientists love a good clean fight. Students of how mammalian “cochlear amplification” comes about have been in the ring for more than 30 years; more than 60 if we consider Gold’s (1948) initial suggestions. The development of two schools of thought, championing outer hair cell (OHC) somatic motility and OHC ciliary motility as the means of amplification, is amply documented and need no review here (Dallos, 2008, Hudspeth, 2008). The common

Coupled hair-bundles could endow the cochlear amplifier with sharp frequency tuning and nonlinear compression

by Kai Dierkes, Benjamin Lindner, Frank Jülicher*

The key signatures of the auditory amplifier are (i) a frequency tuned and sensitive response to weak stimuli, (ii) a compressive nonlinear response over a large amplitude range, and (iii) spontaneous otoacoustic emissions (Dallos, 1992, Hudspeth, 2008). These signatures are reflected in observed basilar-membrane vibrations (Robles and Ruggero, 2001) and can be understood as the consequence of the presence of nonlinear dynamic oscillators

The origin of the cochlear amplifier

by Robert Fettiplace*, Carole M. Hackney

The mammalian cochlea is a unique cellular array the properties of which vary systematically along the organ. These range from the stiffness and size of gross features such as the basilar and tectorial membrane and the dimensions of the outer hair cells (OHCs) (Lim, 1986) to the amplitude of the mechanotransducer channels (Beurg et al., 2006). All features must ultimately conspire to establish the tonotopic map. Passive mechanical tuning is augmented by

A critical need in hearing

by Pascal Martin*, A.J. Hudspeth

One may investigate the basis of the active process in either of two ways. Most studies have focused on the subcellular and molecular details of the candidate mechanisms, membrane-based electromotility and active hair-bundle motility. Despite the present uncertainties in the field, such detailed mechanistic investigations must ultimately reveal the origins of the four cardinal aspects of the active process: amplification, frequency tuning, compressive

Predicting the role of OHC somatic motility and HB motility in cochlear amplification using a mathematical model

by Julien Meaud*, Karl Grosh

The mammalian cochlear amplifier done

by J. Santos-Sacchi

Acknowledgements

Paul Avan, Christine Petit, “Top connectors of the hair-bundle are required for waveform distortion and suppression masking but not cochlear amplification.” This work was supported by the European Commission FP6 Integrated Project EuroHear.

William E. Brownell, “Membrane-based amplification in hearing.” Work supported by research grants R01-DC002775 and DC000354 from NIDCD.

Peter Dallos, “Feedback in the cochlea.” Supported by NIH Grant DC00089-38.

Robert Fettiplace, Carole M. Hackney, “The origin

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