Review series The cell biology of hearing

J. Cell Biol. Vol. 190 No. 1 9–20 www.jcb. org/cgi/doi/10.1083/jcb.201001138 JCB Correspondence to Ulrich Müller: umueller@scripps.edu Abbreviations used in this paper: IHC, inner hair cell; OHC, outer hair cell; PCP, planar cell polarity. Setting the tone: the remarkable properties of the auditory system The inner ear responds to sound-induced vibrations of less than a nanometer, can amplify signals by more than 100-fold, and has a wide dynamic range enabling humans to perceive frequencies from 20 Hz to 20 kHz. Essential for this extraordinary capability are the mechanosensory hair cells, which together with supporting cells and accessory extracellular structures form the organ of Corti within the snail-shaped cochlea of the inner ear (Fig. 1, A and B). The human organ of Corti harbors 16,000 hair cells that are patterned in one row of inner hair cells (IHCs) and three rows of outer hair cells (OHCs; Fig. 1, B and C). Each hair cell contains at the apical surface its mechanically sensitive organelle, the hair bundle, which consists of dozens of stereocilia (Fig. 1, C and D; Fig. 2 A). An extracellular matrix, the tectorial membrane, covers the apical surface of the organ of Corti and is attached to the stereociliary bundles of OHCs. The cell bodies of hair cells form tight connections with support cells, which in turn adhere at their basal surface to an additional extracellular matrix, the basilar membrane (Fig. 1 B). Hearing is initiated when oscillations in air pressure are converted into fluid pressure that travel down the cochlear duct and induce vibrations in the basilar membrane. The vibrations are transferred onto hair cells, leading to deflection of the hair bundles, the opening of mechanically gated ion channels and hair cell depolarization. Because of gradual changes in the features of the organ of Corti, such as the height of stereocilia and the width and thickness of the basilar membrane (Lim, 1980), hair cells at different positions along the cochlear duct are tuned to different frequencies: hair cells at the base of the duct respond to highest frequencies, those at the apex to the lowest frequencies (Liberman, 1982; Müller, 1991, 1996). Active feedback mechanisms must amplify basilar membrane motion because viscous damping in the cochlea would otherwise dissipate sound energy. The underlying process is called the cochlear amplifier and depends on OHCs (Kiang et al., 1986; Dallos, 1992). When passive basilar membrane resonance is induced by a pure tone at its corresponding frequency position along the cochlear duct, OHCs are locally activated and enhance basilar membrane vibration (Rhode, 1971). IHCs detect these vibrations and activate afferent neurons. The cochlear amplifier has a remarkable compressive nonlinearity; this ensures that soft sounds are amplified more strongly than loud sounds (Robles and Ruggero, 2001; Hudspeth, 2008). Dramatic progress has recently been made in our understanding of the molecular mechanisms that regulate auditory sense organ development and function. Progress has largely been driven by the study of genes that are linked to hearing loss, the most common form of sensory impairment in humans (Table I). We will emphasize here advances regarding the cell biology of hair cells. Other recent reviews have summarized the mechanisms that regulate auditory sense organ development and synaptic function and will not be considered (Glowatzki et al., 2008; Kelly and Chen, 2009; Rida and Chen, 2009).