Elsevier

Hearing Research

Volume 279, Issues 1–2, September 2011, Pages 1-12
Hearing Research

Modulation of hair cell efferents

https://doi.org/10.1016/j.heares.2010.12.018Get rights and content

Abstract

Outer hair cells (OHCs) amplify the sound-evoked motion of the basilar membrane to enhance acoustic sensitivity and frequency selectivity. Medial olivocochlear (MOC) efferents inhibit OHCs to reduce the sound-evoked response of cochlear afferent neurons. OHC inhibition occurs through the activation of postsynaptic α9α10 nicotinic receptors tightly coupled to calcium-dependent SK2 channels that hyperpolarize the hair cell. MOC neurons are cholinergic but a number of other neurotransmitters and neuromodulators have been proposed to participate in efferent transmission, with emerging evidence for both pre- and postsynaptic effects. Cochlear inhibition in vivo is maximized by repetitive activation of the efferents, reflecting facilitation and summation of transmitter release onto outer hair cells. This review summarizes recent studies on cellular and molecular mechanisms of cholinergic inhibition and the regulation of those molecular components, in particular the involvement of intracellular calcium. Facilitation at the efferent synapse is compared in a variety of animals, as well as other possible mechanisms of modulation of ACh release. These results suggest that short-term plasticity contributes to effective cholinergic inhibition of hair cells.

Highlights

► Medial olivocochlear efferents produce an inhibitory feedback onto hair cells. ► Colocalization of neurotransmitters suggests a modulation of efferent efficacy. ► Repetitive electrical stimulations of efferent fibers facilitate neurotransmission. ► Short-term synaptic plasticity occurs at medial olivocochlear efferents.

Introduction

Mechanosensory hair cells in the organ of Corti send acoustic information to the brain through synapses with peripheral afferent neurons. In return, feedback provided by efferent neurons located in the brainstem and projecting to the cochlea modulates that afferent activity. Efferent inhibition of the auditory end-organs was first shown by Galambos (1956). Electrical stimulation of the olivocochlear axons reduced the amplitude of the compound action potential (CAP) recorded extracellularly from the VIIIth nerve in response to an acoustic click or brief tone burst. It is now widely accepted that this CAP reduction resulted from medial olivocochlear (MOC) efferent inhibition of the active electromotile response of OHCs that amplifies basilar membrane motion to increase acoustic sensitivity (Brownell et al., 1985, Ashmore, 1987) for review see (Guinan and Stankovic, 1996, Cooper and Guinan, 2006, Ashmore, 2008).

In mammals, the efferent neurons can be classified into two anatomically and functionally distinct groups named according to their origin in the lateral or medial region of the superior olivary complex (Warr and Guinan, 1979): lateral olivocochlear (LOC) efferents project to the region near the inner hair cells (IHCs) and terminate on the dendrites of type I auditory afferents postsynaptic to the IHCs. Medial olivocochlear (MOC) efferents originate in the medial and rostral region of the superior olivary complex and send thicker myelinated axons to innervate predominantly outer hair cells (OHCs) in the mature cochlea as well the IHCs of pre-hearing animals (see for review (Simmons, 2002, Bruce et al., 2000).

This review will summarize physiological studies of efferent inhibition in hair cells of vertebrates ranging from fish to mammals. Studies in the mammalian cochlea focused initially on the transient MOC synapses on immature inner hair cells (IHCs), but improving methodologies have increased attention to older OHCs. However, postsynaptic recordings of LOC effects in type I afferents are only beginning, and so are not available for this review. The interested Reader is referred to previous studies of LOC function (Ruel et al., 2007). The mechanism of cholinergic inhibition is well-conserved among vertebrate hair cells, mediated by an unusual ionotropic ACh receptor and associated calcium-activated potassium channels. In addition, efferent terminals may contain other neurotransmitters, receptors and channels that could modulate synaptic strength. These candidate signaling molecules will be summarized first. Secondly, we will discuss emerging knowledge on the mechanics of synaptic transmission and its modulation by neurotransmitters or small proteins. Short-term facilitation of inhibition has been observed in several species, and may be a fundamental property of efferent feedback. Finally, we review in vivo olivocochlear physiology, in particular those studies providing information on the discharge rate of MOC neurons to assess further the role of activity-dependent plasticity in olivocochlear function.

Section snippets

Cellular mechanism of MOC efferent inhibition

Although recent studies have concentrated on efferent inhibition of mammalian cochlear hair cells, the initial descriptions of cellular mechanisms came from studies in non-mammalian vertebrates. In the lateral line organ of fish (the burbot) electrical stimulation of efferent fibers evoked inhibitory post-synaptic potentials (IPSPs) that hyperpolarized the hair cells and reduced the amplitude of spontaneous or evoked EPSPs recorded from afferent nerve terminals (Flock and Russell, 1976).

Facilitating efferent inhibition in hair cells

Short-term plasticity refers to changes in synaptic efficacy that are induced by repetitive stimulation. Such effects can last from a few milliseconds to a few tens of seconds. Different forms of short-term plasticity elicited by various pattern of stimulation, and differing by their duration have been described: synaptic facilitation, depression, post-tetanic potentiation and augmentation (reviewed by Capogna, 1998, Catterall and Few, 2008). Synaptic facilitation is the only form of short-term

Effect of altering MOC efferent function or innervation

Efferent function in vivo has been studied by surgical ablation, as well as through genetic elimination of essential components. Severing the efferent supply of newborn cats altered afferent response properties (Walsh et al., 1998) but not cochlear afferent innervation, (Liberman et al., 2000) although previous efforts did show elevated afferent innervation to OHCs (Pujol and Carlier, 1982). While potentially revealing, surgical ablation presents substantial experimental challenges. Thus, the

Role of the olivocochlear efferents in hearing

While our knowledge of the cellular mechanisms of MOC efferent physiology has grown considerably in the past two decades, the integration of this knowledge into a broader understanding of audition is a still more challenging task. For example, MOC efferents have been suggested to shift the dynamic range of hearing and to increase the ability to discriminate sounds in a noisy background (anti-masking effect) (for review see Christopher Kirk and Smith, 2003, Guinan, 2006). However, mice lacking

Conclusion

Over the past two decades, considerable progress has been made in determining the cellular and molecular mechanisms of inhibitory feedback onto sensory hair cells. Although ACh is known to support efferent-mediated hair cell inhibition, there are several other neurotransmitters (GABA, CGRP, opioids) colocalized with ACh in the MOC efferent terminals, suggesting modulation of synaptic transmission and the possibility of different forms of synaptic plasticity. The molecular components as well as

Acknowledgements

This work was supported by grants from the National Institute on Deafness and Other Communication Disorders to P. A. F. (R01DC001508) and the Center for Hearing and Balance at Johns Hopkins University (P30DC005211).

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