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Abstract

Exposure to loud sounds is a major hazard in everyday life for citizens of both developed and developing countries. This has become a major health problem since over 250 million people worldwide present hearing disabilities. Single exposures to blasts or acute harming sounds, but also long-term (chronic) expositions to moderate noise can produce long term consequences to hearing. In the past, however, it was considered that the effect of the exposure to noise, called ‘acoustic trauma’, could be temporary if hearing sensitivity was recovered within hours to days. Nonetheless, this idea has been seriously challenged by recent evidence indicating that recovery of hearing thresholds can engulf pathophysiological processes that are only revealed in the long term. The main targets of this type of damage are auditory nerve (AN) neurons that are responsible for bringing acoustic information from the periphery to the brain, and also the sensory cells that are located in the inner ear. Two types of sensory cell co-exist in the mammalian inner ear: inner hair cells (IHC) and outer hair cells (OHC). They are both capable of detecting sounds, but also play different roles in the process of hearing. IHC are responsible for transmitting all acoustic information to the AN neurons by means of specialized synaptic contacts. OHC, on the other hand, are responsible for amplifying sound signals to improve signal detection and also frequency discrimination. As indicated before, AN neurons are one of the main targets of acoustic trauma, in a process that would be initiated by the swelling of their synaptic terminals and the loss of the synaptic contact with IHC. Over years, multiple reports have described the morphological effects of noise exposure on AN neurons and hair cells, but few studies concentrated on the functional aspects of the problem. The main goal of this project is to advance in our knowledge of the physiological consequences of the acoustic trauma, specially investigating the effects on the synaptic function of both IHC and OHC. On Aim 1 of this project, we propose to investigate how the capacity of IHC to release neurotransmitter is affected by noise exposure. In the same path, we will also investigate the cellular mechanisms underpinning dendrite swelling in AN neurons. Does Ca2+ enter during normal synaptic transmission? On Aim 2 of this project, we will specifically study the composition of AMPA receptors subunits that determine the Ca2+ permeability in AN responses to glutamate release. Finally, on Aim 3 we will study a cholinergic feedback loop in the cochlea that was shown to regulate and protect the inner ear from over-excitation. We have recently shown a strong reduction in the number of these synaptic contacts with OHC. Therefore, we will investigate the functionality of the remaining contacts with OHC after noise exposure. Do they show any compensation to the reduction in contact number?