Trends in Neurosciences
ReviewA Bundle of Mechanisms: Inner-Ear Hair-Cell Mechanotransduction
Section snippets
Inner-Ear Mechanosensation
Mechanosensation is one of the oldest sensory modalities, with functions spanning single-cell volume regulation, proprioception, organismal self-localization, and hearing 1, 2, 3, 4, 5. In particular, the vertebrate inner ear houses end organs specialized for sensing motion and sound. Vestibular systems primarily detect nonperiodic signals, arising from head orientation and acceleration, although their sensory hair cells also respond to low-frequency stimuli. In auditory systems, hair cells
The Macroscopic Environment
The environment of sensory hair bundles shapes the signals translated to the MGCs and determines which mechanical cue is best monitored by a particular system (Figure 1). In some hearing organs, hair bundles are freestanding; stimulated and coupled by fluid forces, which intensify with the stimulus frequency. To coordinate their motion in other settings, bundles are embedded in a cupula, tectorial structure, otolithic membrane, or sallet. The mechanical structure of the organ dictates the
Gating-Spring Theory
Because many animals hear high-frequency sounds (>1 kHz), their MGCs must respond quickly to stimulation (<1 ms), implicating direct mechanical coupling between bundle motion and channel gating. The speed of channel gating is set by the channel properties and the mechanical components transmitting force on the bundle to force at the channel.
The opening of the MGCs is concomitant with the extension of an elastic element, known as the gating spring, in series with the channel [22]. Channel opening
Adaptation
Hair-bundle mechanosensitivity is also shaped by an additional dynamic process, termed adaptation, which shifts the operating point of a hair bundle in response to a step stimulus without loss of sensitivity at the new resting position (Figure 4) 44, 45, 46. Adaptation can be envisioned as a change in the force sensed by MGCs that modulates their probability of opening. This process extends the dynamic range of a hair bundle, provides high-pass filtering properties to the hair bundle, and is
Active Signal Detection
Signal detection by hair bundles is limited by intrinsic stochastic fluctuations setting the thresholds of all auditory and vestibular systems [69]. These fluctuations are inherently related to damping [70], which slows responses to stimuli. To encode temporal aspects of a stimulus, hair bundles must respond with sufficient speed and amplitude to elicit a neural response and distinguish external signals from intrinsic noise. Because of these fundamental limits, it is likely that both auditory
Concluding Remarks and Future Perspectives
Although it is clear that the function of auditory and vestibular organs is dictated by the environment and properties of their mechanosensory hair bundles, fundamental questions remain (see Outstanding Questions). Faster and more precise techniques are needed to stimulate mammalian hair bundles [96]. Modeling predicts that a stimulus that better reproduces the natural in vivo input to a hair bundle will lead to faster adaptation time constants and narrower activation curves [20]. Ascertaining
Acknowledgments
This work was supported by NIDCD grants DC003896 and DC014658.
Glossary
- Amplification
- in the context of inner-ear research, refers to a boost in the mechanical response of the living inner ear to stimulation in comparison to immediately post-mortem.
- Activation curve
- the MET current as a function of hair bundle displacement.
- Bifurcation
- a change in the qualitative behavior of a system owing to an alteration in operating point. At a fold bifurcation, a system develops two additional steady states. At a Hopf bifurcation, a system transitions from quiescence to
References (101)
- et al.
Proprioception
Curr. Biol.
(2018) - et al.
Stiffness of sensory-cell hair bundles in the isolated guinea pig cochlea
Hear. Res.
(1984) Underestimated sensitivity of mammalian cochlear hair cells due to splay between stereociliary columns
Biophys. J.
(2015)- et al.
Compliance of the hair bundle associated with gating of mechanoelectrical transduction channels in the bullfrog’s saccular hair cell
Neuron
(1988) TMHS is an integral component of the mechanotransduction machinery of cochlear hair cells
Cell
(2012)TMIE is an essential component of the mechanotransduction machinery of cochlear hair cells
Neuron
(2014)TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear
Neuron
(2013)TMC1 and TMC2 localize at the site of mechanotransduction in mammalian inner ear hair cell stereocilia
Cell Rep.
(2015)Prestin-driven cochlear amplification is not limited by the outer hair cell membrane time constant
Neuron
(2011)Unifying the various incarnations of active hair-bundle motility by the vertebrate hair cell
Biophys. J.
(2007)