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Article

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

by
Philine Marchetta
1,†,
Daria Savitska
1,†,
Angelika Kübler
1,
Giulia Asola
1,
Marie Manthey
1,
Dorit Möhrle
1,
Thomas Schimmang
2,
Lukas Rüttiger
1,
Marlies Knipper
1,* and
Wibke Singer
1
1
Department of Otolaryngology, Head & Neck Surgery, Tübingen Hearing Research Centre (THRC), Molecular Physiology of Hearing, University of Tübingen, Elfriede-Aulhorn-Straße 5, 72076 Tübingen, Germany
2
Instituto de Biologíay Genética Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, E-47003 Valladolid, Spain
*
Author to whom correspondence should be addressed.
†
These authors contributed equally.
Brain Sci. 2020, 10(10), 710; https://doi.org/10.3390/brainsci10100710
Submission received: 27 August 2020 / Revised: 1 October 2020 / Accepted: 2 October 2020 / Published: 6 October 2020
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor in the Auditory System)
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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.
Keywords: central compensation; cochlear synaptopathy; auditory nerve latency; age-related hearing loss; activity dependent BDNF; long term potentiation central compensation; cochlear synaptopathy; auditory nerve latency; age-related hearing loss; activity dependent BDNF; long term potentiation
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MDPI and ACS Style

Marchetta, P.; Savitska, D.; Kübler, A.; Asola, G.; Manthey, M.; Möhrle, D.; Schimmang, T.; Rüttiger, L.; Knipper, M.; Singer, W. Age-Dependent Auditory Processing Deficits after Cochlear Synaptopathy Depend on Auditory Nerve Latency and the Ability of the Brain to Recruit LTP/BDNF. Brain Sci. 2020, 10, 710. https://doi.org/10.3390/brainsci10100710

AMA Style

Marchetta P, Savitska D, Kübler A, Asola G, Manthey M, Möhrle D, Schimmang T, Rüttiger L, Knipper M, Singer W. Age-Dependent Auditory Processing Deficits after Cochlear Synaptopathy Depend on Auditory Nerve Latency and the Ability of the Brain to Recruit LTP/BDNF. Brain Sciences. 2020; 10(10):710. https://doi.org/10.3390/brainsci10100710

Chicago/Turabian Style

Marchetta, Philine, Daria Savitska, Angelika Kübler, Giulia Asola, Marie Manthey, Dorit Möhrle, Thomas Schimmang, Lukas Rüttiger, Marlies Knipper, and Wibke Singer. 2020. "Age-Dependent Auditory Processing Deficits after Cochlear Synaptopathy Depend on Auditory Nerve Latency and the Ability of the Brain to Recruit LTP/BDNF" Brain Sciences 10, no. 10: 710. https://doi.org/10.3390/brainsci10100710

APA Style

Marchetta, P., Savitska, D., Kübler, A., Asola, G., Manthey, M., Möhrle, D., Schimmang, T., Rüttiger, L., Knipper, M., & Singer, W. (2020). Age-Dependent Auditory Processing Deficits after Cochlear Synaptopathy Depend on Auditory Nerve Latency and the Ability of the Brain to Recruit LTP/BDNF. Brain Sciences, 10(10), 710. https://doi.org/10.3390/brainsci10100710

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