Altered cochlear innervation in developing and mature naked and Damaraland mole rats

Abstract

Compared to many other rodent species, naked mole rats (Heterocephalus glaber) have elevated auditory thresholds, poor frequency selectivity, and limited ability to localize sound. Because the cochlea is responsible for encoding and relaying auditory signals to the brain, we used immunofluorescence and quantitative image analysis to examine cochlear innervation in mature and developing naked mole rats compared to mice (Mus musculus), gerbils (Meriones unguiculatus), and Damaraland mole rats (Fukomys damarensis), another subterranean rodent. In comparison to mice and gerbils, we observed alterations in afferent and efferent innervation as well as their patterns of developmental refinement in naked and Damaraland mole rats. These alterations were, however, not always shared similarly between naked and Damaraland mole rats. Most conspicuously, in both naked and Damaraland mole rats, inner hair cell (IHC) afferent ribbon density was reduced, whereas outer hair cell afferent ribbon density was increased. Naked and Damaraland mole rats also showed reduced lateral and medial efferent terminal density. Developmentally, naked mole rats showed reduced and prolonged postnatal reorganization of afferent and efferent innervation. Damaraland mole rats showed no evidence of postnatal reorganization. Differences in cochlear innervation specifically between the two subterranean rodents and more broadly among rodents provides insight into the cochlear mechanisms that enhance frequency sensitivity and sound localization, maturation of the auditory system, and the evolutionary adaptations occurring in response to subterranean environments.

Preparation of the intact rodent organ of Corti for RNAscope and immunolabeling, confocal microscopy, and quantitative analysis

“…(See details provided in the materials and equipment section below). Note: This protocol has been used to isolate the sensory epithelium of various rodents (e.g., Barone et al. 2019 ), including aged rodents.…”

“…No changes in the protocol described here are necessary when using a different strain/line. Moreover, this protocol has been successfully applied to other rodents, including rats (e.g., McLean et al., 2009 ) as well as gerbils and various mole rats ( Barone et al., 2019 , Pyott et al., 2020 ). d Various probes can be used depending on the experimental design.…”

“…The script and complete documentation are provided in the key resources table . This script has been used previously ( Sadeghi et al., 2014 , Ye et al., 2017 , Barone et al., 2019 ).…”

“…Spotty loss of inner and outer hair cells can occur naturally as part age-related hearing loss. Nevertheless, with practice, organs of Corti and regions of intact inner and outer hair cells can be successfully obtained from mice up to two years of age and other even older rodents ( Barone et al., 2019 ).…”

Functional, Morphological, and Evolutionary Characterization of Hearing in Subterranean, Eusocial African Mole-Rats

“…A study using microcomputed tomography concluded that the gross dimensions of the middle and inner ear, including cochlear length, are not sufficient to explain altered hearing in bathyergids [14]. Another study reported alterations in the patterns of innervation of the cochlear hair cells in naked and Damaraland mole-rats (Fukomys damarensis) compared with mice and gerbils, but these alterations are again not sufficient to explain the decreased hearing sensitivity in mole-rats [15]. Finally, the most comprehensive examination of auditory function has been performed in Fukomys anselli.…”