Emergent Phenomena in Cochlear Mechanics
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Emergent Phenomena in Cochlear Mechanics. Christopher A. Shera Eaton-Peabody Laboratory of Auditory Physiology Harvard Medical School. Is it somatic electromotility?. Or active hair-bundle motility?. (Hudspeth 1997). What is the Biophysical Origin of the Cochlear Amplifier?.

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Emergent Phenomena in Cochlear Mechanics

Christopher A. Shera

Eaton-Peabody Laboratory of Auditory Physiology

Harvard Medical School


Is it somatic electromotility?

Or active hair-bundle motility?

(Hudspeth 1997)

What is the Biophysical Origin of the Cochlear Amplifier?


“The rapid conformational change associated with channels closing together tightens tip links and moves the hair bundle by several nanometers. It has been suggested that this mechanism, if timed appropriately to different stimulus frequencies for each hair cell, could amplify the vibration of the cochlea’s basilar membrane (a process termed the ‘cochlear amplifier’). If so, the TRPA1 protein could be at once the hair-cell transduction channel, the gating spring, and the cochlear amplifier.”

“The rapid conformational change associated with channels closing together tightens tip links and moves the hair bundle by several nanometers. It has been suggested that this mechanism, if timed appropriately to different stimulus frequencies for each hair cell, could amplify the vibration of the cochlea’s basilar membrane (a process termed the ‘cochlear amplifier’). If so, the TRPA1 protein could be at once the hair-cell transduction channel, the gating spring, and the cochlear amplifier.”


The Debate is Misleadingly Framed closing together tightens tip links and moves the hair bundle by several nanometers. It has been suggested that this mechanism, if timed appropriately to different stimulus frequencies for each hair cell, could amplify the vibration of the cochlea’s basilar membrane (a process termed the ‘cochlear amplifier’). If so, the TRPA1 protein could be at once the hair-cell transduction channel, the gating spring, and the cochlear amplifier.”

The cochlear amplifier is not

EITHER somatic motility OR hair-bundle motility.

The cochlear amplifier is not BOTH.

The cochlear amplifier is NEITHER.


Insights from Cochlear Modeling closing together tightens tip links and moves the hair bundle by several nanometers. It has been suggested that this mechanism, if timed appropriately to different stimulus frequencies for each hair cell, could amplify the vibration of the cochlea’s basilar membrane (a process termed the ‘cochlear amplifier’). If so, the TRPA1 protein could be at once the hair-cell transduction channel, the gating spring, and the cochlear amplifier.”

Inverse method (e.g., Zweig, de Boer)

Determines functional properties of the organ of Corti from measurements of BM motion


P closing together tightens tip links and moves the hair bundle by several nanometers. It has been suggested that this mechanism, if timed appropriately to different stimulus frequencies for each hair cell, could amplify the vibration of the cochlea’s basilar membrane (a process termed the ‘cochlear amplifier’). If so, the TRPA1 protein could be at once the hair-cell transduction channel, the gating spring, and the cochlear amplifier.”sv

Psv-Psv

=

VBM

Pst

VBM

The Impedance of the Organ of Corti

ZBM(x,f )

= ZPassive + ZActive

Cochlear cross section at location x

What are the relative contributions of the passive and active components?


Passive component closing together tightens tip links and moves the hair bundle by several nanometers. It has been suggested that this mechanism, if timed appropriately to different stimulus frequencies for each hair cell, could amplify the vibration of the cochlea’s basilar membrane (a process termed the ‘cochlear amplifier’). If so, the TRPA1 protein could be at once the hair-cell transduction channel, the gating spring, and the cochlear amplifier.”

Active component

Total (passive & active)

BM-Admittance Frequency Responses


The Impedance of the Organ of Corti closing together tightens tip links and moves the hair bundle by several nanometers. It has been suggested that this mechanism, if timed appropriately to different stimulus frequencies for each hair cell, could amplify the vibration of the cochlea’s basilar membrane (a process termed the ‘cochlear amplifier’). If so, the TRPA1 protein could be at once the hair-cell transduction channel, the gating spring, and the cochlear amplifier.”

ZBM(x,f )

= ZPassive + ZActive

Cochlear cross section at location x


Effects of Fluid Coupling Between the Oscillators closing together tightens tip links and moves the hair bundle by several nanometers. It has been suggested that this mechanism, if timed appropriately to different stimulus frequencies for each hair cell, could amplify the vibration of the cochlea’s basilar membrane (a process termed the ‘cochlear amplifier’). If so, the TRPA1 protein could be at once the hair-cell transduction channel, the gating spring, and the cochlear amplifier.”


The Impedance of the Organ of Corti closing together tightens tip links and moves the hair bundle by several nanometers. It has been suggested that this mechanism, if timed appropriately to different stimulus frequencies for each hair cell, could amplify the vibration of the cochlea’s basilar membrane (a process termed the ‘cochlear amplifier’). If so, the TRPA1 protein could be at once the hair-cell transduction channel, the gating spring, and the cochlear amplifier.”

ZBM(x,f )

= ZPassive + ZActive

Cochlear cross section at location x


Effects of Scalae Height (Nature of Fluid Coupling) closing together tightens tip links and moves the hair bundle by several nanometers. It has been suggested that this mechanism, if timed appropriately to different stimulus frequencies for each hair cell, could amplify the vibration of the cochlea’s basilar membrane (a process termed the ‘cochlear amplifier’). If so, the TRPA1 protein could be at once the hair-cell transduction channel, the gating spring, and the cochlear amplifier.”


^ closing together tightens tip links and moves the hair bundle by several nanometers. It has been suggested that this mechanism, if timed appropriately to different stimulus frequencies for each hair cell, could amplify the vibration of the cochlea’s basilar membrane (a process termed the ‘cochlear amplifier’). If so, the TRPA1 protein could be at once the hair-cell transduction channel, the gating spring, and the cochlear amplifier.”

a force-producing element of

“The rapid conformational change asssociated with channels closing together tightens tip links and moves the hair bundle by several nanometers. It has been suggested that this mechanism, if timed appropriately to different stimulus frequencies for each hair cell, could amplify the vibration of the cochlea’s basilar membrane (a process termed the ‘cochlear amplifier’). If so, the TRPA1 protein could be at once the hair-cell transduction channel, the gating spring, and the cochlear amplifier.”


Ernst Mayr closing together tightens tip links and moves the hair bundle by several nanometers. It has been suggested that this mechanism, if timed appropriately to different stimulus frequencies for each hair cell, could amplify the vibration of the cochlea’s basilar membrane (a process termed the ‘cochlear amplifier’). If so, the TRPA1 protein could be at once the hair-cell transduction channel, the gating spring, and the cochlear amplifier.”

Principle of Emergence

In a structured system, new properties emerge at higher levels of integration which could not have been predicted from a knowledge of the lower-level components.


Spontaneous Otoacoustic Emissions (SOAEs) closing together tightens tip links and moves the hair bundle by several nanometers. It has been suggested that this mechanism, if timed appropriately to different stimulus frequencies for each hair cell, could amplify the vibration of the cochlea’s basilar membrane (a process termed the ‘cochlear amplifier’). If so, the TRPA1 protein could be at once the hair-cell transduction channel, the gating spring, and the cochlear amplifier.”

(Allen et al. 1995)


Gold’s (1948) Local-Oscillator Model closing together tightens tip links and moves the hair bundle by several nanometers. It has been suggested that this mechanism, if timed appropriately to different stimulus frequencies for each hair cell, could amplify the vibration of the cochlea’s basilar membrane (a process termed the ‘cochlear amplifier’). If so, the TRPA1 protein could be at once the hair-cell transduction channel, the gating spring, and the cochlear amplifier.”

“…if the feedback ever exceeded the losses, then a resonant element [in the organ of Corti] would become self-oscillatory, and oscillations would build up [to] a level where linearity was not preserved.”

“In spite of [the] self-regulating mechanism we might expect that occasional disturbances would bring an element into the region of self-oscillation, when it is normally so close to this condition. If this occurred, then we should hear a clear note which would persist until the adjusting mechanism has regained control, or until the nervous sensitivity has decreased sufficiently.”


Spontaneous Hair-Bundle Oscillations closing together tightens tip links and moves the hair bundle by several nanometers. It has been suggested that this mechanism, if timed appropriately to different stimulus frequencies for each hair cell, could amplify the vibration of the cochlea’s basilar membrane (a process termed the ‘cochlear amplifier’). If so, the TRPA1 protein could be at once the hair-cell transduction channel, the gating spring, and the cochlear amplifier.”

(Martin et al. 2001, 2003)


Oscillation/SOAE frequencies are determined by cellular properties such as

  • Hair-bundle stiffness and geometry

  • Gating compliance

  • Adaptation and/or transduction kinetics

  • Ca2+ equilibration kinetics

Models for Hair-Bundle Oscillators

(Hudspeth 1997)


The hair bundle is both the source of SOAEs and the motor element of the cochlear amplifier

SOAEs Used to Argue Against Somatic Motility as the “Active Process” in Mammalian Hearing

  • The motor element of the cochlear amplifier is the source of SOAEs

  • Unprovoked mechanical oscillations of the motor element underlie the production of SOAEs

  • Although hair bundles can oscillate spontaneously, no spontaneous OHC contractions have ever been observed


Gold’s Local-Oscillator Model Gets the Chain of Causality Exactly Backwards

The ear does not produce SOAEs because hair cells oscillate spontaneously.

Rather, hair cells oscillate spontaneously (in vivo) because the ear produces SOAEs.


Kemp’s (1979) Global Standing-Wave Model Exactly Backwards

SOAEs are continuously self-evoking stimulus-frequency otoacoustic emissions (SFOAEs)

  • initiated either by sounds from the environment or by physiological noise




Spacetime Diagram Illustrating Standing Waves Exactly Backwards

Spacetime Diagram Illustrating SFOAE Generation


Effective Reflection Coefficients Exactly Backwards

For ingoing-waves at stapes:

For outgoing-waves at stapes:



Spontaneous Otoacoustic Emissions Exactly Backwards

(Allen et al. 1995)




9 ears in 9 subjects Exactly Backwards

(Data from Shera & Guinan 2003 and Dreisbach et al. 1998)


Human SOAE Spacings Exactly Backwards

556 SOAE pairs 73 ears 47 subjects

(Data from Talmadge et al. 1993 and Burns et al. 1992)


Variability of SOAE Spacings Exactly Backwards


The global standing-wave model correctly predicts: Exactly Backwards

  • Multiple SOAEs with a characteristic minimum frequency spacing

  • The mean value of this spacing

  • Its standard deviation

  • Its power-law dependence on frequency

  • The magnitude, sign, and frequency dependence of SOAE frequency shifts induced by modulations in middle-ear stiffness

Summary of Results

Predictions arise naturally in the standing-wave framework but require ad-hoc adjustment of local-oscillator models.


Autonomous oscillators are cells or subcellular structures Exactly Backwards

Autonomous oscillator is the cochlea as a whole

Macromechanical structures and processes play no fundamental role: They simply provide a conduit for energy to escape from the cochlea

Macromechanical structures and processes determine SOAE characteristics (e.g., SOAEs would not occur if Rstapes=0)

SOAE frequencies are set by local properties of hair cells (e.g., hair-bundle geometry, transduction kinetics, etc)

SOAE frequencies are set by global properties (e.g., round-trip traveling-wave phase shifts, middle-ear impedance, etc)

Local-Oscillator vs Global Standing-Wave SOAEs

Local-Oscillator

Global Standing-Wave



Hudspeth and colleagues have repeatedly invoked Gold’s local-oscillator model to argue that OHC somatic motility is unlikely to constitute the “active process” in mammalian hearing (e.g., Martin & Hudspeth 1999, 2001; Martin et al. 2001, 2003; Duke 2002; Jülicher et al 2003).

  • Based on the apparent absence of spontaneous OHC contractions

But Hudspeth’s argument that

“unprovoked mechanical oscillations of some constituent of the inner ear must underlie the production of spontaneous otoacoustic emissions”

is based on a logical fallacy.

Implications for the Cellular Basis of the Cochlear Amplifier


Ernst Mayr local-oscillator model to argue that OHC somatic motility is unlikely to constitute the “active process” in mammalian hearing (e.g., Martin & Hudspeth 1999, 2001; Martin et al. 2001, 2003; Duke 2002; Jülicher et al 2003).

The Principle of Emergence

In a structured system, new properties emerge at higher levels of integration which could not have been predicted from a knowledge of the lower-level components.

The local-oscillator model gets the causality exactly backwards…

SOAEs arise through the collective action of the entire cochlea.

Spontaneous emission of sound from the ear does not require the autonomous mechanical oscillation of its cellular constituents.


The whole is more than the sum of its parts. local-oscillator model to argue that OHC somatic motility is unlikely to constitute the “active process” in mammalian hearing (e.g., Martin & Hudspeth 1999, 2001; Martin et al. 2001, 2003; Duke 2002; Jülicher et al 2003).

Since the interactions are usually nonlinear, the collective behavior cannot be obtained by summing the behaviors of the isolated parts.

The whole obeys different laws than the parts.

Its behavior can be described by “macrolaws” without recourse to the detailed microlaws that govern the behavior of the components.

Characteristics of Emergent Phenomena

Emergence occurs when a relatively small number of copies of relatively simple components are coupled together in relatively simple ways.

The parts acquire new properties by virtue of their embedding in the whole.

Context and coupling are crucial.


Conjecture: The problem is artificial because the solution is “emergent.”

When embedded in situ, OHCs have an effective response bandwidth much greater than they do in isolation.

Basic idea proposed long ago by modelers (e.g., Mountain & Hubbard 1994); for latest experimental evidence, see Scherer & Gummer, 2004.

The OHC Membrane Time-Constant Problem


The Crucial Role of Mathematical is “emergent.”

Modeling in the Study of Hearing


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