Age-Dependent Auditory Processing Deficits after Cochlear Synaptopathy Depend on Auditory Nerve Latency and the Ability of the Brain to Recruit LTP/BDNF.

Philine Marchetta,Marie Manthey,Lukas Rüttiger,Thomas Schimmang,Marlies Knipper,Dorit Möhrle,Giulia Asola,Angelika Kübler,Wibke Singer,Daria Savitska

doi:10.3390/brainsci10100710

Abstract

Age-related decoupling of auditory nerve fibers from hair cells (cochlear synaptopathy) has been linked to temporal processing deficits and impaired speech recognition performance. The link between both is elusive. We have previously demonstrated that cochlear synaptopathy, if centrally compensated through enhanced input/output function (neural gain), can prevent age-dependent temporal discrimination loss. It was also found that central neural gain after acoustic trauma was linked to hippocampal long-term potentiation (LTP) and upregulation of brain-derived neurotrophic factor (BDNF). Using middle-aged and old BDNF-live-exon-visualization (BLEV) reporter mice we analyzed the specific recruitment of LTP and the activity-dependent usage of Bdnf exon-IV and -VI promoters relative to cochlear synaptopathy and central (temporal) processing. For both groups, specimens with higher or lower ability to centrally compensate diminished auditory nerve activity were found. Strikingly, low compensating mouse groups differed from high compensators by prolonged auditory nerve latency. Moreover, low compensators exhibited attenuated responses to amplitude-modulated tones, and a reduction of hippocampal LTP and Bdnf transcript levels in comparison to high compensators. These results suggest that latency of auditory nerve processing, recruitment of hippocampal LTP, and Bdnf transcription, are key factors for age-dependent auditory processing deficits, rather than cochlear synaptopathy or aging per se.

Highlights

Aging people often experience difficulties in perceiving speech in a noisy environment, even without elevated audiometric thresholds [1]
The results demonstrated that only animals with a reduced neural gain over age showed a loss of temporal resolution in auditory processing [6], suggesting neural gain and not cochlear synaptopathy per se as a key factor for temporal processing
Old BLEV mice showed a significant increase in threshold compared with young and middle-aged animals measured by click-evoked auditory brainstem responses (ABR) (Figure 1a; all statistical findings and details of the tests can be found in the figure legends and in Table 1), noise-burst stimuli (Figure 1b), and pure tone frequencies (Figure 1c)

Summary

Introduction

Aging people often experience difficulties in perceiving speech in a noisy environment, even without elevated audiometric thresholds [1]. Older people who have maintained good hearing sensitivity, frequently report difficulties in acoustically complex environments This general profile of auditory deficiency, which can occur in individuals with a normal audiogram, is supposed to reflect impaired processing of acoustic temporal cues due to cochlear synaptopathy [8,9]. It was hypothesized that a reduction in the viable population of auditory nerve fibers over age [5,10], of the subpopulation of fibers with a low spontaneous firing rate (low-SR) and a high threshold, might lead to auditory deficits at supra-threshold levels and in challenging listening situations such as in the presence of background noise [2,5,6,11,12,13]. Unlike fibers with a high spontaneous firing rate (high-SR) and a low threshold, low-SR fibers do not contribute to auditory threshold sensitivity [4,5,10]

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Discussion

Conclusion