Sound exposure dynamically induces dopamine synthesis in cholinergic LOC efferents for feedback to auditory nerve fibers
Abstract
Lateral olivocochlear (LOC) efferent neurons modulate auditory nerve fiber (ANF) activity using a large repertoire of neurotransmitters, including dopamine (DA) and acetylcholine (ACh). Little is known about how individual neurotransmitter systems are differentially utilized in response to the ever-changing acoustic environment. Here we present quantitative evidence in rodents that the dopaminergic LOC input to ANFs is dynamically regulated according to the animal's recent acoustic experience. Sound exposure upregulates tyrosine hydroxylase, an enzyme responsible for dopamine synthesis, in cholinergic LOC intrinsic neurons, suggesting that individual LOC neurons might at times co-release ACh and DA. We further demonstrate that dopamine down-regulates ANF firing rates by reducing both the hair cell release rate and the size of synaptic events. Collectively, our results suggest that LOC intrinsic neurons can undergo on-demand neurotransmitter re-specification to re-calibrate ANF activity, adjust the gain at hair cell/ANF synapses, and possibly to protect these synapses from noise damage.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Source data file has been provided for Figure 4B.
Article and author information
Author details
Funding
National Institute on Deafness and Other Communication Disorders (R01DC006476)
- Elisabeth Glowatzki
National Institute on Deafness and Other Communication Disorders (R01DC012957)
- Elisabeth Glowatzki
National Institute on Deafness and Other Communication Disorders (R01DC017620)
- Amanda M Lauer
National Institute on Deafness and Other Communication Disorders (R01DC016641)
- Amanda M Lauer
David M. Rubenstein Fund for Hearing Research
- Amanda M Lauer
Capita Foundation
- Amanda M Lauer
Korea Health Industry Development Institute (Korea Health Technology R&D Project HI17C0952)
- Eunyoung Yi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All procedures concerning animals were performed in accordance with animal protocols approved by the Johns Hopkins University Animal Care and Use Committee (IACUC). The Johns Hopkins University Office of Laboratory Animal Welfare (OLAW) Assurance number is A-3272-01.
Copyright
© 2020, Wu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.