Understanding the mechanisms underlying noise-induced damage of hair cell ribbon synapses

Age-related hearing loss (ARHL) is a progressive form of hearing loss and is one of the most common sensory deficits and health conditions in the elderly. Approximately half of all adults in their seventh decade exhibit hearing loss that affect their daily lives. This is further associated with significant psychological and medical morbidity, including social isolation, frailty and depression.

The number of people with hearing loss is increasing. It is expected that more than 15 million people in the UK will be affected by hearing loss by 2050, the majority of which will be related to ageing (World Health Organisation). However, the mechanisms underlying ARHL remain poorly understood. This is partly because ARHL is a complex disorder with many contributing factors, including genetic predisposition and environmental factors such as noise exposure. Noise exposure is known to accelerate the onset and progression of ARHL but the mechanisms by which this occurs are largely unknown.

In the mammalian cochlea, sound is transduced by sensory cells called hair cells. These cells form specialised synapses, called ribbon synapses, which are the sites of neurotransmitter release onto auditory afferent neurons. Information such as sound intensity and timing is encoded by these synapses into neural activity, which is required for us to perceive sound. A lot of recent evidence has shown that ribbon synapses are the first structures within the cochlea to be lost after noise exposure, which is likely to be the primary cause of hearing loss in these cases. I hypothesise that when the hair cells are over-stimulated by noise they release an excessive amount of glutamate, which causes toxicity by activating calcium-dependent proteases (excitotoxicity). Therefore, the aim of this project is to investigate how synaptic transmission is affected by noise insult in the mammalian cochlea.

Using both ex vivo and in vivo approaches, I will determine the level of glutamate release that is...