Olivocochlear efferent effects on perception and behavior

Highlights

• Efferent auditory pathways reach the cochlea through the olivocochlear (OC) system.

• The OC system plays a role in hearing in noise and selective attention.

• Methodological limitations and compensatory processes limit observed effects.

• Additional studies of the effects of the OC system on behavior are necessary.

Abstract

The role of the mammalian auditory olivocochlear efferent system in hearing has long been the subject of debate. Its ability to protect against damaging noise exposure is clear, but whether or not this is the primary function of a system that evolved in the absence of industrial noise remains controversial. Here we review the behavioral consequences of olivocochlear activation and diminished olivocochlear function. Attempts to demonstrate a role for hearing in noise have yielded conflicting results in both animal and human studies. A role in selective attention to sounds in the presence of distractors, or attention to visual stimuli in the presence of competing auditory stimuli, has been established in animal models, but again behavioral studies in humans remain equivocal. Auditory processing deficits occur in models of congenital olivocochlear dysfunction, but these deficits likely reflect abnormal central auditory development rather than direct effects of olivocochlear feedback. Additional proposed roles in age-related hearing loss, tinnitus, hyperacusis, and binaural or spatial hearing, are intriguing, but require additional study. These behavioral studies almost exclusively focus on medial olivocochlear effects, and many relied on lesioning techniques that can have unspecific effects. The consequences of lateral olivocochlear and of corticofugal pathway activation for perception remain unknown. As new tools for targeted manipulation of olivocochlear neurons emerge, there is potential for a transformation of our understanding of the role of the olivocochlear system in behavior across species.

Introduction

Our ability to effectively perceive and interact with the environment integrates the activity of efferent pathways that can modulate the signals transmitted by the afferent sensory systems. In the auditory system, the efferent pathways form a neural network comprised of several feedback loops with numerous subcortical nuclei, including the thalamus, inferior colliculus, superior olivary complex, and cochlear nucleus (Malmierca and Ryugo, 2011). The auditory efferent pathways extend from auditory cortex to the peripheral sensory organ via the olivocochlear (OC) system (Fig. 1). The OC system, originally described by Rasmussen (1946), is formed by two neuronal groups: (i) the medial olivocochlear neurons (MOC) and (ii) the lateral olivocochlear neurons (LOC) (Warr and Guinan, 1979).

Even though the precise anatomical location of these two groups varies depending on the species, in general MOC neurons can be found in the medial periolivary regions, while the LOCs originate in or around the lateral superior olive (Brown, 2011). The MOC synapses are organized along a tonotopic gradient in the periphery, with greater density in the middle regions of the cochlea (Guinan, 1996; Maison et al., 2003). In addition, most of the MOC neurons send collaterals that reach the CN of the same side as the target cochlea (Benson and Brown, 1990). MOC neurons primarily release acetylcholine, leading to the hyperpolarization of the OHCs and, consequently, a reduction of the gain of the cochlear amplifier (Blanchet et al., 1996; Dallos et al., 1997; Evans et al., 2000).

LOC neurons are on average smaller and more numerous than MOCs and are characterized by having fine, non-myelinated fibers (Guinan, 1996). As with the MOCs, they also project via the vestibular nerve, but synapse with the dendrites of type I cochlear afferents just below the inner hair cells (Guinan, 1996). These projections are tonotopically organized and almost all of them (95–100%) are ipsilateral (Schofield, 2010). LOC neurons express a greater diversity of neurotransmitters than MOCs. While the majority of LOC neurons are cholinergic, they have been observed to express other neurotransmitters within the same synaptic terminal including dopamine (DA), calcitonin gene-related peptide (CGRP), GABA and opioid peptides such as enkephalin (Ciuman, 2010; Eybalin et al., 1993; Reijntjes and Pyott, 2016; Wu et al., 2020b). Furthermore, in mice there is some evidence of subgroups of dopaminergic LOC neurons that are not cholinergic (Darrow et al., 2006b).

The physiological effects of activating the OC system have been reviewed in detail in recent reviews (e.g., Terreros and Delano 2015; Guinan 2018; Lopez-Poveda 2018; Fuchs and Lauer 2018). In spite of the fact that the OC system is composed of both MOC and LOC neurons, most of the knowledge about OC physiology has been obtained by electrical stimulation of MOC fibers (e.g., Galambos 1956; Fex 1959; Guinan and Gifford 1988, Cooper and Guinan, 2006; Elgueda et al., 2011). The electrical activation of MOC fibers at the floor of the fourth ventricle reduced the amplitude of auditory nerve responses (Galambos, 1956) and increases the magnitude of cochlear microphonics (CM) potentials (Fex, 1959; Elgueda et al., 2011). MOC neurons can be reflexively activated by ipsilateral and contralateral sounds (Buño, 1978; Liberman, 1989) through a brainstem circuit that includes auditory nerve, cochlear nucleus and MOC neurons (Thompson and Thompson 1991; DeVenecia et al., 2005). In contrast to the middle ear muscle reflexes (stapedius and tensor tympani), the MOC reflex can be elicited by lower level sounds (< 60 dB), producing a suppression of cochlear responses that can be measured non-invasively with otoacoustic emissions or with electrocochleography (Liberman and Guinan, 1998; Aedo et al., 2015). One important caveat is that this reflex is highly variable among different individuals, ranging from large suppressions (up to 10 dB of effective attenuation) to no effect or even enhancements, although most studies show a limited range of otoacoustic suppression effects within only 1–2 dB in humans (Puria et al., 1996; Maison and Liberman, 2000). This may be due to the relatively weak innervation of outer hair cells by MOC neurons in humans compared to common laboratory species (Liberman and Liberman 2019). The inter-individual variability has been correlated with levels of resistance to acoustic injury and to different capacities to suppress auditory distractors during selective attention (Maison and Liberman 2000; Bowen et al., 2020). Otoacoustic suppression effects may underestimate the true size of the effect. Some studies measuring MOC-induced CAP suppression in humans show much larger effects (Smith et al., 2017), whereas other studies have only shown small suppressive effects only after many hours of testing (Lichtenhan et al., 2016). The size of the observed effects likely depends on the specific testing parameters used (Verschooten et al., 2017).

Much of what we know about how the OC system affects behavior comes from studies of its dysfunction. Conflicting results have sometimes been reported in behavioral studies performed in humans and animals. Here we focus on the behavioral effects of OC efferent activation, de-efferentation, and genetic manipulation. We include evoked potential studies in cases where little or no behavioral evidence is available, as these data are useful in making predictions about behavioral function.