Coupling and Elastic Loading Affect the Active Response by the Inner Ear Hair Cell Bundles

Active hair bundle motility has been proposed to underlie the amplification mechanism in the auditory endorgans of non-mammals and in the vestibular systems of all vertebrates, and to constitute a crucial component of cochlear amplification in mammals. We used semi-intact in vitro preparations of the bullfrog sacculus to study the effects of elastic mechanical loading on both natively coupled and freely oscillating hair bundles. For the latter, we attached glass fibers of different stiffness to the stereocilia and observed the induced changes in the spontaneous bundle movement. When driven with sinusoidal deflections, hair bundles displayed phase-locked response indicative of an Arnold Tongue, with the frequency selectivity highest at low amplitudes and decreasing under stronger stimulation. A striking broadening of the mode-locked response was seen with increasing stiffness of the load, until approximate impedance matching, where the phase-locked response remained flat over the physiological range of frequencies. When the otolithic membrane was left intact atop the preparation, the natural loading of the bundles likewise decreased their frequency selectivity with respect to that observed in freely oscillating bundles. To probe for signatures of the active process under natural loading and coupling conditions, we applied transient mechanical stimuli to the otolithic membrane. Following the pulses, the underlying bundles displayed active movement in the opposite direction, analogous to the twitches observed in individual cells. Tracking features in the otolithic membrane indicated that it moved in phase with the bundles. Hence, synchronous active motility evoked in the system of coupled hair bundles by external input is sufficient to displace large overlying structures.

[1]  Frank Jülicher,et al.  Unifying the various incarnations of active hair-bundle motility by the vertebrate hair cell. , 2007, Biophysical journal.

[2]  K. Arisaka,et al.  Correlated movement of hair bundles coupled to the otolithic membrane in the bullfrog sacculus , 2009, Hearing Research.

[3]  M O Magnasco,et al.  A model for amplification of hair-bundle motion by cyclical binding of Ca2+ to mechanoelectrical-transduction channels. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[4]  A. Hudspeth.  Making an Effort to Listen: Mechanical Amplification in the Ear , 2008, Neuron.

[5]  L. Robles,et al.  Mechanics of the mammalian cochlea. , 2001, Physiological reviews.

[6]  Multiple-timescale dynamics underlying spontaneous oscillations of saccular hair bundles. , 2011, Biophysical journal.

[7]  B. Kendall.  Nonlinear Dynamics and Chaos , 2001 .

[8]  D. Corey,et al.  Ca2+ changes the force sensitivity of the hair-cell transduction channel. , 2006, Biophysical journal.

[9]  R. Eatock,et al.  Adaptation in hair cells. , 2000, Annual review of neuroscience.

[10]  S. Strogatz,et al.  Amplitude death in an array of limit-cycle oscillators , 1990 .

[11]  Frank Jülicher,et al.  A critique of the critical cochlea: Hopf--a bifurcation--is better than none. , 2010, Journal of neurophysiology.

[12]  Alan R. Champneys,et al.  What Fire is in Mine Ears: Progress in Auditory Biomechanics , 2011 .

[13]  F. Jülicher,et al.  Auditory sensitivity provided by self-tuned critical oscillations of hair cells. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[14]  A J Hudspeth,et al.  Active hair-bundle movements can amplify a hair cell's response to oscillatory mechanical stimuli. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R. Fettiplace,et al.  The mechanical properties of ciliary bundles of turtle cochlear hair cells. , 1985, The Journal of physiology.

[16]  E. Lewis,et al.  The vertebrate ear as an exquisite seismic sensor. , 1984, The Journal of the Acoustical Society of America.

[17]  G. Manley,et al.  Evidence for an active process and a cochlear amplifier in nonmammals. , 2001, Journal of neurophysiology.

[18]  A. Hudspeth,et al.  Hair-bundle movements elicited by transepithelial electrical stimulation of hair cells in the sacculus of the bullfrog , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[19]  A J Hudspeth,et al.  Compressive nonlinearity in the hair bundle's active response to mechanical stimulation , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Michael C. Mackey,et al.  From Clocks to Chaos , 1988 .

[21]  Dynamic state and evoked motility in coupled hair bundles of the bullfrog sacculus , 2010, Hearing Research.

[22]  Peter G. Gillespie,et al.  Hair-Cell Mechanotransduction and Cochlear Amplification , 2005, Neuron.

[23]  Yasuo Harada,et al.  The otolithic membrane , 1983 .

[24]  E. Lewis.  Tuning in the bullfrog ear. , 1988, Biophysical journal.

[25]  D. Corey,et al.  The micromachinery of mechanotransduction in hair cells. , 2007, Annual review of neuroscience.

[26]  A J Hudspeth,et al.  Rapid, Active Hair Bundle Movements in Hair Cells from the Bullfrog’s Sacculus , 1996, The Journal of Neuroscience.

[27]  Bechara Kachar,et al.  Structural basis for mechanical transduction in the frog vestibular sensory apparatus: I. The otolithic membrane , 1990, Hearing Research.

[28]  Distribution of frequencies of spontaneous oscillations in hair cells of the bullfrog sacculus. , 2009, Biophysical journal.

[29]  Vladimir Igorevich Arnold,et al.  Geometrical Methods in the Theory of Ordinary Differential Equations , 1983 .

[30]  M. Alexander,et al.  Principles of Neural Science , 1981 .

[31]  A. Hudspeth,et al.  Essential nonlinearities in hearing. , 2000, Physical review letters.

[32]  Frank Jülicher,et al.  Active hair-bundle motility harnesses noise to operate near an optimum of mechanosensitivity. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[33]  E R Lewis,et al.  Inner ear: dye injection reveals peripheral origins of specific sensitivities. , 1982, Science.

[34]  Robert Fettiplace,et al.  Depolarization of Cochlear Outer Hair Cells Evokes Active Hair Bundle Motion by Two Mechanisms , 2006, The Journal of Neuroscience.

[35]  P. Avan,et al.  The remarkable cochlear amplifier , 2010, Hearing Research.

[36]  Thomas F. Weiss,et al.  Static material properties of the tectorial membrane: a summary , 2003, Hearing Research.

[37]  A J Hudspeth,et al.  Spontaneous Oscillation by Hair Bundles of the Bullfrog's Sacculus , 2003, The Journal of Neuroscience.

[38]  E R Lewis,et al.  Morphological Basis for a Mechanical Linkage in Otolithic Receptor Transduction in the Frog , 1971, Science.

[39]  A J Ricci,et al.  Active Hair Bundle Motion Linked to Fast Transducer Adaptation in Auditory Hair Cells , 2000, The Journal of Neuroscience.

[40]  Naoum P. Issa,et al.  Hair-bundle stiffness dominates the elastic reactance to otolithic-membrane shear , 1993, Hearing Research.

[41]  Benjamin Lindner,et al.  Coupling a sensory hair-cell bundle to cyber clones enhances nonlinear amplification , 2010, Proceedings of the National Academy of Sciences.

[42]  R. Rabbitt,et al.  Mechanical amplification by hair cells in the semicircular canals , 2010, Proceedings of the National Academy of Sciences.

[43]  Benjamin Lindner,et al.  Enhancement of sensitivity gain and frequency tuning by coupling of active hair bundles , 2008, Proceedings of the National Academy of Sciences.