Project Summary / Abstract: Auditory Mechanics and Cochlear Amplification 2020 Sound input to the cochlea causes a frequency-sorted wave-pattern of sensory tissue motion that conveys sound information to the auditory neurons, leading to hearing. A currently untreatable aspect of hearing impairment is the deterioration of the cochlea's ability to sharply separate sound by frequency. The cochlea's healthy frequency tuning is largely provided by the cochlear amplifier, an outer-hair-cell-driven, place-frequency-localized electromechanical feedback mechanism that is both powerful and fragile. This project's aims 1-3 explore the cell/structure basis of cochlear amplification. The studies use intracochlear sensors and a cutting-edge imaging and vibrometry technology, spectral-domain optical-coherence-tomography (SD-OCT). Localized measurements of mechanical and electrical responses at and within the cochlea's sensory tissue will be made both in healthy normal and in modified cochleae. Gerbils and guinea pigs are used and critical aspects of cochlear amplification are compared in the two species in aim 2. In aim 1, measurements are made in cochleae before and after intracochlear injection of substances that will modify tectorial membrane (TM) mechanics. Because it governs transduction in hair cells, the TM plays a profound role in cochlear amplification; our studies test hypotheses that are based on cochlear models and measurements in isolated TMs and in TM-mutant mice. Aim 3 makes use of SD-OCT's penetrating abilities to test previously untestable fluid-mechanical properties of the organ of Corti. Aim 4 explores the transmission of sound to the cochlea by the middle ear, and how this transmission is modified by feedback from the middle ear muscle, tensor tympani. In preliminary work, tensor tympani modified transmission in a subtle, frequency-dependent manner that could be involved in focusing on particular sound sources, for example during communication. Experiments in which tensor tympani is tensed with voltage pulses will determine how the muscle affects the transmitted sound signal.