Age-Related Hearing Loss: Sensory and Neural Etiology and Their Interdependence

Abstract

Age-related hearing loss (ARHL) is a common, increasing problem for older adults, affecting about 1 billion people by 2050. We aim to correlate the different reductions of hearing from cochlear hair cells (HCs), spiral ganglion neurons (SGNs), cochlear nuclei (CN), and superior olivary complex (SOC) with the analysis of various reasons for each one on the sensory deficit profiles. Outer HCs show a progressive loss in a basal-to-apical gradient, and inner HCs show a loss in a apex-to-base progression that results in ARHL at high frequencies after 70 years of age. In early neonates, SGNs innervation of cochlear HCs is maintained. Loss of SGNs results in a considerable decrease (~50% or more) of cochlear nuclei in neonates, though the loss is milder in older mice and humans. The dorsal cochlear nuclei (fusiform neurons) project directly to the inferior colliculi while most anterior cochlear nuclei reach the SOC. Reducing the number of neurons in the medial nucleus of the trapezoid body (MNTB) affects the interactions with the lateral superior olive to fine-tune ipsi- and contralateral projections that may remain normal in mice, possibly humans. The inferior colliculi receive direct cochlear fibers and second-order fibers from the superior olivary complex. Loss of the second-order fibers leads to hearing loss in mice and humans. Although ARHL may arise from many complex causes, HC degeneration remains the more significant problem of hearing restoration that would replace the cochlear implant. The review presents recent findings of older humans and mice with hearing loss.

Developmental eye motion plasticity after unilateral embryonic ear removal in Xenopus laevis

“…Ontogenetic development of brainstem vestibular circuits might be highly plastic and can be exploited to drive functionally appropriate motor outputs despite lacking peripheral sensors. Considerations to such plasticity extents would be beneficial for targeted therapeutics, such as those aimed at using transplantation approaches to replace vestibular deficits ( Elliott et al., 2022 ), and might aid in the holistic understanding of adaptability in vestibular development and processing.…”

Neurosensory development of the four brainstem-projecting sensory systems and their integration in the telencephalon

“…Future differentiation will generate a large set of cochlear nuclei that must be traced from the earliest gene expression to establish into bushy, globular, spherical, stellate, and pyramidal neurons (Malmierca, 2015;Oertel and Cao, 2020). In addition, unipolar brush cells, granule cells, and fusiform cells develop in the DCN; each is uniquely positive for calbindin, calretinin, and parvalbumin (reviewed in Caspary and Llano, 2018;Elliott et al, 2022b).…”

“…Different projections innervate ipsi-and contralateral MOCs (Marrs et al, 2013;Lipovsek and Wingate, 2018;Kandler et al, 2020;Grothe, 2021). For example, the development of detailed innervation shows an exuberant innervation of the MNTB followed by the development of the calyx of Held with time (Holcomb et al, 2013) that may decline in density formation with age (Elliott et al, 2022b). SGN fibers end up in a tonotopic organization that follows a base to apex progression to the MOCs.…”

Strategies of developmental vestibular plasticity after unilateral embryonic ear removal in Xenopus laevis

“…Ontogenetic development of brainstem vestibular circuits is therefore highly plastic and can be exploited to drive functionally appropriate motor outputs despite lacking canonical peripheral sensors. Considerations to such plasticity extents would be beneficial for targeted therapeutics, such as those aimed at using transplantation approaches to replace vestibular deficits (Elliott et al, 2022), and might aid in the holistic understanding of adaptability in vestibular development and processing.…”