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.

eLife digest

Every day, we hear sounds that might be alarming, distracting, intriguing or calming – or simply just too loud. Our hearing system responds to these acoustic changes by fine-tuning sounds before they enter the brain. For example, if a noise is too loud, the volume can be turned down by dampening the signals nerve fibers in the ear send to the brain. This is thought to reduce the damage loud sounds can cause to the sensory organ inside the ear.

A set of nerve cells located at the base of the brain called the lateral olivocochlear (LOC) neurons coordinate this adjustment to different volumes and sounds. When these neurons receive information on external sounds, they signal back to the hearing organs and adjust the activity of auditory nerve fibers that communicate this information to the brain. LOC neurons use a diverse range of molecules to modify the activity of auditory nerve fibers, including the ‘feel-good’ neurotransmitter dopamine. But it is unclear what role dopamine plays in this auditory feedback loop.

To find out, Wu et al. studied the hearing system of mice that had been exposed to different levels of sound. This involved imaging LOC neurons stained with a marker for dopamine and measuring the activity of nerve fibers in the inner ear. The experiments showed that LOC neurons in mice that had recently been exposed to sound were covered in an enzyme that is essential for making dopamine. The louder the sound, the more of this enzyme was present, suggesting that the amount of dopamine released depends on the volume of the sound.

LOC neurons release another neurotransmitter called acetylcholine, which stimulates activity in auditory nerve fibers. Wu et al. found that dopamine and acetylcholine are released from the same group of LOC neurons. However, dopamine had the opposite effect to acetylcholine and reduced nerve activity. These findings suggest that by controlling the mixture of neurotransmitters released, LOC neurons are able to fine-tune the activity of auditory nerve fibers in response to acoustic changes.

This work provides a new insight into how our hearing system is able to perceive and relay changes in the sound environment. A better understanding of this auditory feedback loop could influence the design of implant devices for people with impaired hearing.