Title: Experimental Study of Nonlinearity and Amplification in the Mammalian Cochlea
Description: The mammalian hearing organ, the cochlea, has a marvelous sensitivity and frequency resolution. Due to passive mechanical properties (e.g. mass, stiffness, damping), sound-induced traveling waves are formed on the basilar membrane (BM), which are longitudinally tuned to different frequencies. In a live cochlea, a phenomenon called cochlear amplification, derived from the mechano-electric transduction of the outer hair cells (OHCs), locally enhances the traveling wave and increases the frequency selectivity. My research during the PhD program was focused on studying the in-vivo mechanical and electrophysiological responses of the cochlea in animal models.In the first set of experiments, the intra-cochlear motion and the OHC-generated local cochlear microphonic (LCM) responses were measured in the base of the gerbil cochlea. We used optical coherence tomography (OCT) to measure the intra-cochlear motion and a tungsten micro-electrode to obtain the LCM responses. We explored the effect of the two types of sound stimuli, single and multi-tone stimuli, to the nonlinear behavior of the LCM and the intra-cochlear motion responses in two frequency bands: a frequency band in which cochlear responses show a nonlinear peak (the best frequency (BF) band) and a frequency range below the large peak (sub-BF band: f < ∼ 0.7 × BF).

In the sub-BF band, BM motion had linear growth for both stimulus types, and the motion in the OHC region was mildly nonlinear for single tones, and relatively strongly nonlinear for multi-tones. Sub-BF, the nonlinear character of the LCM was similar to that of the OHC- region motion. In the BF band, the LCM and the intra-cochlear motions all possessed the BF peak nonlinearity. Coupling these observations with previous findings on phasing between OHC force and traveling wave motions, we proposed the following framework for cochlear nonlinearity: The BF-band nonlinearity is an amplifying nonlinearity, in which OHC forces input power into the traveling wave, allowing it to travel further apical to the region where it peaks. The sub-BF nonlinearity is a non- amplifying nonlinearity; it represents OHC electromotility, and saturates due to OHC current saturation, but the OHC forces do not possess the proper phasing to feed power into the traveling wave. In the second set of experiments, we repeated the cochlear measurements as in the first project in the base of guinea pig cochlea.

The goal was to compare the degree of nonlinearity and amplification in the LCM and intra-cochlear responses between gerbil and guinea pig. The experimental condition and method were similar to the gerbil study. In the BF band, our observations were similar to our previous measurements in gerbil: a nonlinear peak in LCM responses and in intra- cochlear displacements, and higher motion in the OHC region than the BM. Sub-BF, the responses in the two species were different. In both species the BM motion responses in the sub-BF band was linear and LCM was nonlinear. Sub-BF in the OHC-region, nonlinearity was only observed in a subset of healthy guinea pig cochleae while in gerbil, robust nonlinearity was observed in all healthy cochleae. The differences suggest that gerbils and guinea pigs may employ different mech- anisms for to achieve frequency selectivity. However, it cannot be ruled out that the differences are due to technical measurement differences across the species.