Olivocochlear Changes Associated With Aging Predominantly Affect the Medial Olivocochlear System

Age-related hearing loss (ARHL) is a public health problem that has been associated with negative health outcomes ranging from increased frailty to an elevated risk of developing dementia. Significant gaps remain in our knowledge of the underlying central neural mechanisms, especially those related to the efferent auditory pathways. Thus, the aim of this study was to quantify and compare age-related alterations in the cholinergic olivocochlear efferent auditory neurons. We assessed, in young-adult and aged CBA mice, the number of cholinergic olivocochlear neurons, auditory brainstem response (ABR) thresholds in silence and in presence of background noise, and the expression of excitatory and inhibitory proteins in the ventral nucleus of the trapezoid body (VNTB) and in the lateral superior olive (LSO). In association with aging, we found a significant decrease in the number of medial olivocochlear (MOC) cholinergic neurons together with changes in the ratio of excitatory and inhibitory proteins in the VNTB. Furthermore, in old mice we identified a correlation between the number of MOC neurons and ABR thresholds in the presence of background noise. In contrast, the alterations observed in the lateral olivocochlear (LOC) system were less significant. The decrease in the number of LOC cells associated with aging was 2.7-fold lower than in MOC and in the absence of changes in the expression of excitatory and inhibitory proteins in the LSO. These differences suggest that aging alters the medial and lateral olivocochlear efferent pathways in a differential manner and that the changes observed may account for some of the symptoms seen in ARHL.

Efferent feedback controls bilateral auditory spontaneous activity

In the developing auditory system, spontaneous activity generated in the cochleae propagates into the central nervous system to promote circuit formation. The effects of peripheral firing patterns on spontaneous activity in the central auditory system are not well understood. Here, we describe wide-spread bilateral coupling of spontaneous activity that coincides with the period of transient efferent modulation of inner hair cells from the brainstem medial olivocochlear system. Knocking out α9/α10 nicotinic acetylcholine receptors, a requisite part of the efferent pathway, profoundly reduces bilateral correlations. Pharmacological and chemogenetic experiments confirm that the efferent system is necessary for normal bilateral coupling. Moreover, auditory sensitivity at hearing onset is reduced in the absence of pre-hearing efferent modulation. Together, these results demonstrate how afferent and efferent pathways collectively shape spontaneous activity patterns and reveal the important role of efferents in coordinating bilateral spontaneous activity and the emergence of functional responses during the prehearing period.

Click evoked Middle Ear Muscle Reflex: Implications for Medial Olivocochlear System Assays

This study describes a time series-based method of middle ear muscle reflex (MEMR) detection using bilateral clicks, with implications for otoacoustic emission (OAE)-based medial olivocochlear reflex (MOCR) assays. Although current click-based methods can detect changes in the OAE evoking stimulus to monitor the MEMR, these methods do not discriminate between true MEMR-mediated vs. artifactual changes in the stimulus. We measured MEMR in 20 young clinically normal hearing individuals using a series of clicks presented at six levels (65 to 95 dB peak-to-peak SPL in 6 dB steps). Results were well-approximated by double-exponential functions. The change in ear canal pressure due to MEMR increased monotonically as a function of click level but non-monotonically with frequency. MEMR thresholds estimated using this method were lower than that obtained from a clinical tympanometer in ~94% of the participants. It is recommended that the OAE-evoking stimulus be monitored to determine the presence of MEMR across a wide band of frequencies in MOCR assays. A time series-based method, along with statistical tests, may provide additional confidence in detecting the MEMR. MEMR effects were smallest at 2 kHz which may provide avenues for minimizing the MEMR influence on the MOCR.

Hyperactivity in the medial olivocochlear efferent system is a common feature of tinnitus and hyperacusis in humans

Tinnitus and hyperacusis are common, burdensome sources of morbidity with a high rate of co-occurrence. Knudson et al. ( J Neurophysiol 112: 3197–3208, 2014) demonstrated that efferent suppression of cochlear activity by the medial olivocochlear system is enhanced in individuals with tinnitus and/or hyperacusis. Their findings stress that atypical activity in the efferent auditory pathway may represent a shared substrate, as well as a potential therapeutic target, in tinnitus and hyperacusis.