Published August 13, 2024 | Version v1
Preprint Open

Toward an In Vitro Preparation to Study the Cochlear Active Process of Mammals

  • 1. ROR icon Rockefeller University
  • 2. ROR icon Howard Hughes Medical Institute

Description

The mammalian cochlea is powered by 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 criticality also underpins the active process of the mammalian cochlea. To probe this question, we conducted electrophysiological recordings of microphonic signals in isolated cochlear segments of the Mongolian gerbil. We did so by improving the two-compartment cochlear preparation originally developed by Chan and Hudspeth to more closely simulate in vivo conditions. 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 pressure influence the electrical response. These changes enabled us to reliably measure compressive nonlinearities with a one-third power law similar to that observed in intact cochleas in vivo.

Abstract (English)

The mammalian cochlea is powered by 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 criticality also underpins the active process of the mammalian cochlea. To probe this question, we conducted electrophysiological recordings of microphonic signals in isolated cochlear segments of the Mongolian gerbil. We did so by improving the two-compartment cochlear preparation originally developed by Chan and Hudspeth to more closely simulate in vivo conditions. 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 pressure influence the electrical response. These changes enabled us to reliably measure compressive nonlinearities with a one-third power law similar to that observed in intact cochleas in vivo.

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