Amplification lags nonlinearity in the recovery from reduced endocochlear potential

Abstract

The mammalian hearing organ, the cochlea, contains an active amplifier to boost the vibrational response to low level sounds. Hallmarks of this active process are sharp location-dependent frequency tuning and compressive nonlinearity over a wide stimulus range. The amplifier relies on outer hair cell (OHC) generated forces driven in part by the endocochlear potential (EP), the ~ +80 mV potential maintained in scala media, generated by the stria vascularis. We transiently eliminated the EP in vivo by an intravenous injection of furosemide and measured the vibrations of different layers in the cochleas organ of Corti using optical coherence tomography. Distortion product otoacoustic emissions (DPOAE) were monitored at the same times. Following the injection, the vibrations of the basilar membrane lost the best frequency (BF) peak and showed broad tuning similar to a passive cochlea. The intra-organ of Corti vibrations measured in the region of the OHCs lost their BF peak and showed low-pass responses, but retained nonlinearity, indicating that OHC electromotility was still operational. Thus, while electromotility is presumably necessary for amplification, its presence is not sufficient for amplification. The BF peak recovered nearly fully within 2 hours, along with a non-monotonic DPOAE recovery that suggests that physical shifts in operating condition are a final step in the recovery process. SIGNIFICANCEThe endocochlear potential, the +80 mV potential difference across the fluid filled compartments of the cochlea, is essential for normal mechanoelectrical transduction, which leads to receptor potentials in the sensory hair cells when they vibrate in response to sound. Intracochlear vibrations are boosted tremendously by an active nonlinear feedback process that endows the cochlea with its healthy sensitivity and frequency resolution. When the endocochlear potential was reduced by an injection of furosemide, the basilar membrane vibrations resembled those of a passive cochlea, with broad tuning and linear scaling. The vibrations in the region of the outer hair cells also lost the tuned peak, but retained nonlinearity at frequencies below the peak, and these sub-BF responses recovered fairly rapidly. Vibration responses at the peak recovered nearly fully over 2 hours. The staged vibration recovery and a similarly staged DPOAE recovery suggests that physical shifts in operating condition are a final step in the process of cochlear recovery.