2025-09-10 ロックフェラー大学
<関連情報>
- https://www.rockefeller.edu/news/38213-researchers-keep-a-mammalian-cochlea-alive-outside-the-body-for-the-first-time/
- https://www.pnas.org/doi/10.1073/pnas.2503389122
- https://www.sciencedirect.com/science/article/pii/S0378595525001066?via%3Dihub
哺乳類蝸牛における局所的臨界挙動による増幅 Amplification through local critical behavior in the mammalian cochlea
Rodrigo G. Alonso, Francesco Gianoli, Brian Fabella, and A. J. Hudspeth
Proceedings of the National Academy of Sciences Published:July 14, 2025
DOI:https://doi.org/10.1073/pnas.2503389122
Significance
Uniquely among our sensory organs, the ear expends energy to amplify the very stimuli that it detects. This “active process” endows the cochlea with exceptional sensitivity, sharp frequency tuning, and broad dynamical range—yet its workings remain elusive. To date, the cochlea’s fragility and inaccessibility have confined studies in vivo, where global phenomena confound local dynamics. Bridging the gap between cellular and whole-organ behavior, we introduce a preparation that preserves the active process ex vivo in a cochlear segment and thus overcome a long-lasting experimental barrier. We show that the active process operates locally and that the sensory epithelium operates near criticality at a Hopf bifurcation. This result reveals a unified biophysical principle that underlies hearing across insects, nonmammalian vertebrates, and mammals alike.
Abstract
Hearing hinges upon the ear’s ability to enhance its responsiveness by means of an energy-expending active process that amplifies the very mechanical inputs that it detects. This process is defined by four properties that, although seemingly unrelated, consistently occur together: amplification, sharp frequency tuning, compressive nonlinearity, and spontaneous otoacoustic emission. In nonmammal tetrapods, the active process is evident in individual hair cells. The hair bundles of the bullfrog, for example, exhibit all four attributes by operating near a Hopf bifurcation—a critical regime in which these properties naturally coalesce. In mammals, however, the delicate nature of the cochlea has restricted the evidence for an active process to studies in vivo, where it is generally attributed to the collective effort of the outer hair cells that energize the traveling wave along the cochlear spiral. As a result, the cellular mechanisms that underlie the properties of mammalian hearing remain contested, with uncertainty about whether criticality plays a role in the cochlea’s active process. Here we show that, when placed in a recording chamber that closely mimics the in vivo physiological environment, a segment of the mammalian cochlea ex vivo displays the features of the active process—amplification, frequency tuning, compressive nonlinearity, and the generation of distortion products. We show that this process operates locally, independently of traveling waves, and that the sensory epithelium achieves active amplification by operating near criticality at a Hopf bifurcation. The results reveal the existence of a unified biophysical principle that underlies auditory processing across species and even phyla.
哺乳類の蝸牛活動過程の研究のための体外準備に向けて Toward an ex vivo preparation for studies of the cochlear active process in mammals
Francesco Gianoli, Rodrigo Alonso, Brian Fabella, A.J. Hudspeth
Hearing Research Available online: 24 April 2025
DOI:https://doi.org/10.1016/j.heares.2025.109288
Highlights
- Ex vivo cochlear preparations exhibit compressive nonlinearity.
- Cochlear microphonics display a 1/3 power-law of compressive growth as a function of sound pressure.
- An imposed artificial endocochlear potential is necessary for compressive nonlinearity.
- Changes in static pressure across the cochlear partition modulates microphonic responses.
- Findings align with theoretical predictions for a system operating near a Hopf bifurcation.
Abstract
The mammalian cochlea benefits from an active process characterized by amplification of mechanical inputs, sharp frequency selectivity, compressive nonlinearity, and spontaneous otoacoustic emission. Similar traits are observed in individual hair cells of nonmammalian tetrapods, in which they emerge from the critical dynamical regime of hair cells operating near a Hopf bifurcation. It remains unclear whether a similar critical regime also underpins the active process of the mammalian cochlea. Efforts to address this question have been limited in part by the absence of an ex vivo preparation that both preserves the physiological integrity of the sensory epithelium and grants direct experimental access to it. To overcome these problems, we improved a two-compartment cochlear preparation (Chan and Hudspeth, 2005a, 2005b) to more closely simulate in vivo conditions and used it to conduct electrophysiological recordings of microphonic signals in isolated cochlear segments of the Mongolian gerbil. Our methodological advances included refining the dissection protocol to reduce the size of the exposed cochlear segment and altering the ionic compositions of the solutions to better control the Ca2+ concentration. We also maintained a constant temperature in order to stabilize the experimental conditions. Most critically, by introducing a mechanism to adjust the pressure in the endolymphatic compartment, we were able to explore how variations in transepithelial pressure influence the electrical response. These changes enabled us to reliably measure compressive nonlinearities with a one-third power law similar to that observed from cochleas in vivo and consistent with the behavior of a dynamical system operating near a Hopf bifurcation.
