The endocochlear potential as an indicator of reticular lamina integrity after noise exposure in mice

Abstract

The endocochlear potential (EP) provides part of the electrochemical drive for sound-driven currents through cochlear hair cells. Intense noise exposure (110 dB SPL, 2 h) differentially affects the EP in three inbred mouse strains (C57BL/6 [B6], CBA/J [CBA], BALB/cJ [BALB]) (Ohlemiller and Gagnon, 2007, Hearing Research 224:34–50; Ohlemiller et al., 2011, JARO 12:45–58). At least for mice older than 3 mos, B6 mice are unaffected, CBA mice show temporary EP reduction, and BALB mice may show temporary or permanent EP reduction. EP reduction was well correlated with histological metrics for injury to stria vascularis and spiral ligament, and little evidence was found for holes or tears in the reticular lamina that might ‘short out’ the EP. Thus we suggested that the genes and processes that underlie the strain EP differences primarily impact cochlear lateral wall, not the organ of Corti. Our previous work did not test the range of noise exposure conditions over which strain differences apply. It therefore remained possible that the relation between exposure severity and acute EP reduction simply has a higher exposure threshold in B6 mice compared to CBA and BALB. We also did not test for age dependence. It is well established that young adult animals are especially vulnerable to noise-induced permanent threshold shifts (NIPTS). It is unknown, however, whether heightened vulnerability of the lateral wall contributes to this condition. The present study extends our previous work to multiple noise exposure levels and durations, and explicitly compares young adult (6–7 wks) and older mice (>4 mos). We find that the exposure level-versus-acute EP relation is dramatically strain-dependent, such that B6 mice widely diverge from both CBA and BALB. For all three strains, however, acute EP reduction is greater in young mice. Above 110 dB SPL, all mice exhibited rapid and severe EP reduction that is likely related to tearing of the reticular lamina. By contrast, EP-versus-noise duration examined at 104 dB suggested that different processes contribute to EP reduction in young and older mice. The average EP falls to a constant level after ~7.5 min in older mice, but progressively decreases with further exposure in young mice. Confocal microscopy of organ of Corti surface preparations stained for phalloidin and zonula occludens-1 (ZO-1) indicated this corresponds to rapid loss of outer hair cells (OHCs) and formation of both holes and tears in the reticular lamina of young mice. In addition, when animals exposed at 119 dB were allowed to recover for 1 mo, only young B6 mice showed collapse of the EP to ≤5 mV. Confocal analysis suggested novel persistent loss of tight junctions in the lateral organ of Corti. This may allow paracellular leakage that permanently reduces the EP. From our other findings, we propose that noise-related lateral wall pathology in young CBA and BALB mice promotes hair cell loss and opening of the reticular lamina. The heightened vulnerability of young adult animals to noise exposure may in part reflect sp...

The Stress Response in the Non-sensory Cells of the Cochlea Under Pathological Conditions—Possible Role in Mediating Noise Vulnerability

“…Our findings of noise-induced acute stress response in the lateral wall of CBA, but not B6 mice correspond to previous studies showing an acute EP drop in noiseexposed CBA mice exclusively (Wang et al 2002;Hirose and Liberman 2003;Ohlemiller and Gagnon 2007;Ohlemiller et al 2018). The question is then whether the acute stress response/EP drop axis is linked with the observed heightened noise vulnerability of OHCs of CBA mice.…”

“…However, this possibility is still to be directly shown by relevant mutant mouse models. It is to be noted that a recent study suggested that lateral wall pathology drives OHC loss particularly in young adult CBA mice, which were also used in the current study, while older CBA mice are less affected (Ohlemiller et al 2018).…”

Inhibition of Histone Methyltransferase G9a Attenuates Noise-Induced Cochlear Synaptopathy and Hearing Loss

“…The changes seen in marginal cells may depend on the strain examined. A recent report showed that noise-exposed CBA/J mice results in temporary EP reduction, while the same is not true for C57B6 mice (Ohlemiller et al 2018). Therefore, the strial effects of noise in the present findings may be characteristic for CBA/J mice but not of some other strains.…”

Onset kinetics of noise-induced purinergic adaptation of the ‘cochlear amplifier’

“…The EP is a biopotential within scala media (~+ 100 mV) that complements the negative membrane potential of the hair cells to provide the driving force for outer hair cell forward and reverse transduction [36,37]. Many studies, using guinea pigs or mice, have shown that the much higher noise levels than those used in the present study are required to cause a sustained drop in EP (~98 dB SPL; [38][39][40][41][42][43][44][45]). Moreover, Hirose and Liberman [45] showed that despite a temporary threshold shift of 40 dB after 94 dB SPL noise exposure for 2 h, the EP was unaffected in CBA/CaJ mice.…”