Olivocochlear Changes Associated With Aging Predominantly Affect the Medial Olivocochlear System

Abstract

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.

Effects of Noise Exposure and Aging on Behavioral Tone Detection in Quiet and Noise by Mice

“…We did not observe the instability of detection in noise that reportedly occurs before overt threshold shifts in C57BL/6 mice with hereditary, early-onset hearing loss ( Prosen et al, 2003 ), possibly because of the abrupt nature of noise-induced hearing damage. Intriguingly, the C56BL/6 strain shows weak medial olivocochlear activity compared with CBA mice even at young ages, although both strains exhibit medial olivocochlear degeneration with age ( Frisina et al, 2007 ; Sinclair et al, 2017 ; Vicencio-Jimenez et al, 2021 ).…”

Alpha9alpha10 knockout mice show altered physiological and behavioral responses to signals in masking noise

“…To overcome this limitation, future experiments could make use of virally introduced genetic gain-of-function mutations (Zhang et al, 2023), inducible gene knockouts, DREADDS, or optogenetic stimulation or silencing of medial olivocochlear neurons in adult animals. Additionally, potential compensatory mechanisms such as lateral olivocochlear plasticity should be further investigated, as these mechanisms have important implications for listeners with degenerating medial olivocochlear systems due to age, noise, and other damaging circumstances (Lauer, 2017; Lauer et al, 2022; Vicencio-Jimenez et al, 2021).…”

“…ABR testing procedures were similar to those previously described in this laboratory (e.g. Capshaw et al, 2022; Vicencio-Jimenez et al, 2021). Briefly, ABR testing was conducted in a sound-treated booth (Industrial Acoustics Company (IAC), Bronx, NY; 59” x 74” x 60”) lined with acoustic foam (Pinta Acoustic, Minneapolis, MN).…”

Editorial: Commonalities and Differences in Vestibular and Auditory Pathways

“…Efferent inputs are required for normal function of the vestibular (Hubner et al, 2015 ; Raghu et al, 2019 ) and auditory pathways (Glowatzki and Fuchs, 2000 ; Maison et al, 2006 ; Johnson et al, 2013 ) and play a role in aging (Lauer et al, 2012 ; Zachary and Fuchs, 2015 ; Fuchs and Lauer, 2019 ; Boero et al, 2020 ; Vicencio-Jimenez et al, 2021 ). In this collection, Lorincz et al provide a detailed map of central and peripheral projections of cholinergic vestibular efferent neurons in mice, using state of the art methods, including transgenic mice and Cre-dependent adeno-associated virus mediated expression of fluorescent reporters.…”