Ultrastructural changes at auditory nerve synapses following moderate noise exposure

Moderate noise exposure is a common experience, yet its impact on central auditory synapses remains poorly understood. We study this issue at the first synapses in the central auditory pathway formed by auditory nerve afferents onto bushy cells in the cochlear nucleus, called endbulbs of Held. Non-traumatic noise exposure alters endbulb properties, decreasing the probability of vesicle release and enlarging the pool of releasable vesicles as assessed using electrophysiological methods and immunolabelling. These changes appear homeostatic, to maintain synaptic efficacy during periods of high activity. To identify structural changes underlying the larger vesicle pool, we used serial blockface electron microscopy of endbulbs from control and noise-exposed mice to quantitatively assess synaptic morphology. We observed no differences in the juxtapositional area between endbulbs and bushy cells, nor in the number or density of active zones and postsynaptic densities. Images of endbulb terminals were significantly darker after noise exposure, indicating an increase in the density of synaptic vesicles. These results suggest that moderate noise exposure induces an activity-dependent increase in presynaptic vesicle numbers, consistent with the observed physiological changes in neurotransmitter release. This work sets the stage for high-resolution studies to quantify docked and reserve vesicles. Significance statementNoise exposure is a fact of everyday life, and it is important to understand how noise affects function in the auditory pathway in the brain to understand the full consequences of noise exposure. Electrophysiological experiments indicate that noise triggers a homeostatic increase in the releasable pool of vesicles at auditory nerve synapses. We examined the cellular basis for this change using serial blockface electron microscopy of auditory nerve synapses with and without noise exposure. We reconstructed a number of bushy cells and their presynaptic auditory nerve terminals. After noise exposure, there was no significant increase in the area of synaptic contact or the number or density of synaptic release sites. There was an increase in the number of vesicles near release sites, which may account for the physiological changes. These results emphasize the importance of detailed anatomical studies to study the effects of noise exposure and thus determine the best mechanistic approach for therapies and treatments of noise-induced hearing loss.