Elsevier

Hearing Research

Volume 303, September 2013, Pages 20-29
Hearing Research

Review
Lead roles for supporting actors: Critical functions of inner ear supporting cells

https://doi.org/10.1016/j.heares.2013.01.008Get rights and content

Abstract

Many studies that aim to investigate the underlying mechanisms of hearing loss or balance disorders focus on the hair cells and spiral ganglion neurons of the inner ear. Fewer studies have examined the supporting cells that contact both of these cell types in the cochlea and vestibular end organs. While the roles of supporting cells are still being elucidated, emerging evidence indicates that they serve many functions vital to maintaining healthy populations of hair cells and spiral ganglion neurons. Here we review recent studies that highlight the critical roles supporting cells play in the development, function, survival, death, phagocytosis, and regeneration of other cell types within the inner ear. Many of these roles have also been described for glial cells in other parts of the nervous system, and lessons from these other systems continue to inform our understanding of supporting cell functions.

This article is part of a Special Issue entitled “Annual Reviews 2013”.

Highlights

► Supporting cells are vital to the development and function of hair cells and neurons. ► Supporting cells mediate hair cell survival, death, and regeneration. ► Supporting cells eliminate damaged or dying hair cells from the sensory epithelium. ► Many functions of supporting cells are similar to those reported for glial cells.

Introduction

Hearing loss affects nearly 4 million American children and 36 million adults (NIDCD, 2010; NIDCD, 2006). Aging, noise trauma, ototoxic drugs, and hereditary mutations are all causes of hearing loss (Li-Korotky, 2012; Seixas et al., 2012; Cheng et al., 2009; Friedman and Griffith, 2003), a condition that has limited treatments and no known cure. In addition, in the United States, balance disorders affect over 600,000 individuals and similarly have few treatment options (NIDCD, 2010). Many studies aimed at understanding the mechanisms underlying hearing loss and balance disorders have focused on mechanosensory hair cells, the sensory receptor cells of the auditory and vestibular systems (Phillips et al., 2008). Fewer studies have examined the biology and functions of the supporting cells that surround hair cells. This review will discuss the emerging evidence indicating that auditory and vestibular supporting cells serve many critical functions, some of which are similar to functions carried out by glial cells (astrocytes, microglia, Schwann cells and oligodendrocytes), suggesting that supporting cells may represent a type of specialized glia.

The mammalian cochlea contains several types of supporting cells, each with a distinct morphology and a specific anatomical location within the organ of Corti (reviewed in Raphael and Altschuler, 2003). Deiters' cells provide structural support for the outer hair cells, which are positioned atop and in direct contact with the Deiters' cell layer (reviewed in Raphael and Altschuler, 2003). Pillar cells form the tunnel of Corti, which lies between the inner and outer hair cells. Hensen's and Claudius cells both lie lateral to the outer hair cells in the outer sulcus. Supporting cells are less well-characterized than hair cells and in striving for better characterization, analogies have been drawn between supporting cells of the inner ear and those of other sensory systems, including the olfactory sustentacular cells and the retinal Müller glia (Rubel et al., 1991). Some similarities and significant differences between auditory supporting cells and these other sensory supporting cell types will be discussed in this review.

Emerging evidence suggests that auditory and vestibular supporting cells serve important functions as mediators of hair cell development, function, death and phagocytosis (Tritsch et al., 2007; Jagger and Forge, 2006; Bird et al., 2010; Lahne and Gale, 2008). Recent reports also indicate that supporting cells may mediate the survival and function of SGNs (Zilberstein et al., 2012). Many of these supporting cell functions are paralleled by glia in their relationship with neurons. Glial cells support neuronal function and survival in many ways. For example, both astrocytes and oligodendrocytes provide trophic support for neurons (Wilkins et al., 2003; Banker, 1980). Astrocytes support neuronal function and survival by clearing glutamate from neuronal synapses (Rothstein et al., 1996) and buffering potassium through a system of gap junctions (reviewed in Leis et al., 2005). Microglia play critical roles in the response to neuronal injury, engulfing apoptotic neurons in the central nervous system (reviewed in Napoli and Neumann, 2009). Following neuronal death in the fish retina, Müller glia serve as neural precursors for regenerated retinal neurons and photoreceptors (Bermingham-McDonogh and Reh, 2011). Many of these functions of glial cells are similar to those that have been described for auditory and vestibular supporting cells.

Section snippets

Development and survival of hair cells and spiral ganglion neurons

In the developing mammalian cochlea, the onset of neuronal activity results from coordinated signaling from hair cells, supporting cells, and SGNs. Cochlear hair cells are depolarized upon deflection of their stereocilia (Flock, 1965; Russell et al., 1986), which triggers the release of glutamate from inner hair cells (IHCs) (Kataoka and Ohmori, 1994). Glutamate binds to synaptic receptors on adjacent SGNs, resulting in the generation of action potentials and transmission of the afferent signal

Hair cell death and survival

Auditory hair cells are both very sensitive in terms of detecting sound and also highly susceptible to damage. The mechanisms that determine whether a hair cell under stress ultimately lives or dies are only beginning to be understood. Recent studies have revealed some of the molecular signals that are activated in supporting cells in response to hair cell damage, and these findings suggest that supporting cells may act as critical mediators of hair cell death (reviewed in Gale and Jagger, 2010

Hair cell regeneration

While the mature mammalian vestibular system exhibits a limited capacity for hair cell regeneration, spontaneous hair cell regeneration has not been reported in the mature organ of Corti (Li and Forge, 1997; Zheng et al., 1999; Yamasoba and Kondo, 2006; Warchol et al., 1993). However, non-mammalian vertebrates have the capacity for robust regeneration of lost hair cells. The first reports of hair cell regeneration in birds were published in the 1980's (Cotanche, 1987; Corwin and Cotanche, 1988;

Summary

Supporting cells play many important roles in the inner ear, and some of those functions are analogous to those of glia in the central nervous system. During development, supporting cells are thought to mediate spontaneous inward currents in hair cells and SGN firing of rapid action potentials, which may be essential to develop neural connections and refine the tonotopic map of the cochlea. Supporting cells provide critical trophic factors to SGNs and are responsible for clearing

Acknowledgments

The authors would like to thank Dr. Doris Wu, Dr. Matthew Kelley, Dr. Meghan Drummond, and Dr. Jonathan Bird for their helpful comments and suggestions on the manuscript. The authors are also grateful to Dr. Jonathan Gale for many thoughtful conversations about supporting cells as well as constructive notes on the development of the text and figures of this manuscript. This work was supported by the NIDCD Division of Intramural Research.

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