Sound exposure dynamically induces dopamine synthesis in cholinergic LOC efferents for feedback to auditory nerve fibers.

Jingjing Sherry Wu,Marco Manca,Hamad Javaid,Eunyoung Yi,Amanda M Lauer,Elisabeth Glowatzki

doi:10.7554/elife.52419

Jingjing Sherry Wu, Marco Manca + Show 4 more

Open Access

https://doi.org/10.7554/elife.52419

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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.

Highlights

In our daily lives, we are routinely exposed to a constantly changing acoustic environment, for example while walking from the office to the cafeteria or from home to our commute
To investigate the extent of dopaminergic efferent inputs to the cochlea, dopaminergic lateral olivocochlear (LOC) fibers were labeled in whole-mount preparations of C57BL/6J mouse cochleas by immunostaining against tyrosine hydroxylase (TH), an enzyme essential for the synthesis of dopamine
Sound exposure dynamically regulates TH expression in LOC intrinsic neurons This study provides several lines of evidence that sound exposure regulates TH expression in LOC intrinsic neurons in a level-dependent and dynamic manner

Summary

Introduction

We are routinely exposed to a constantly changing acoustic environment, for example while walking from the office to the cafeteria or from home to our commute. In response to sound exposure, TH is upregulated in central and peripheral components of cholinergic LOC intrinsic neurons in a frequency and sound level-dependent manner These results imply that the same LOC neurons at times may co-release ACh and DA onto ANFs, most likely resulting in complex changes at multiple sites of the IHC afferent synapses that influence firing rates and dynamic range of ANFs. Electrophysiological data show that DA reduces ANF firing rate by two mechanisms: 1) by reducing the presynaptic release rate, and 2) by reducing the EPSC amplitude and area, thereby most likely reducing the percentage of EPSPs that activate APs. Electrophysiological data show that DA reduces ANF firing rate by two mechanisms: 1) by reducing the presynaptic release rate, and 2) by reducing the EPSC amplitude and area, thereby most likely reducing the percentage of EPSPs that activate APs Taken together, these data suggest that LOC neurons can dynamically adjust their dopamine release to change the gain at hair cell/ANF synapses

Results

Discussion

Materials and methods