This is a Discovery Research Grant awarded to Dr Philippe Vincent at Johns Hopkins University, USA, in 2024.
Background
Sounds from the outside world are detected by sensory cells in the cochlea of the inner ear – these cells are known as inner hair cells. These inner hair cells transform sound information (vibrations in the air) into electrical signals that the brain can interpret and transmit this information to the brain via the auditory nerve.
The cells of the auditory nerve that inner hair cells transmit information to are called spiral ganglion neurons; they are separated from inner hair cells by a tiny gap called a synapse. To transmit the sound information to the spiral ganglion neuron and on into the brain, hair cells release chemicals called neurotransmitters into the synapse.
These chemicals diffuse across the gap and activate the spiral ganglion neuron, which reacts by transmitting the sound information further into the brain. In the brain, this information is interpreted so that you can perceive, understand, and localise sounds.
Depending on how loud the original sound is, the inner hair cells release more or fewer neurotransmitters into the synapse – fewer for quiet sounds, more for louder sounds. Very loud sounds, such as those experienced at music concerts, in nightclubs, at roadworks or construction sites, or even sirens from ambulances, can damage your hearing by overstimulating the inner hair cells.
This causes them to release excessive levels of neurotransmitters into the synapses, damaging them and the spiral ganglion neurons on the other side. The loss of these synapses can cause your hearing to gradually decline over time, but at first, the damage may not be obvious: this is what we call ‘hidden hearing loss.’
Aims
Currently, there are no treatments that can repair the damage to the inner hair cell synapses caused by exposure to loud noise. In this project, the researchers aim to develop tools that the hearing research community can use to develop and test potential new drug treatments that can restore the synapses between inner hair cells and spiral ganglion neurons but even more importantly, restore their correct function.
Studies in other mammalian species, such as mice and gerbils, have shown that these synapses can spontaneously reform after noise trauma, with the degree of regeneration depending on the level of noise exposure. However, these studies were unable to determine whether the regenerated synapses function correctly.
In this project, the researchers will study inner hair cells from mice that have been engineered to produce a light-sensitive protein. They will use light to activate these inner hair cells to release neurotransmitters, similar to the way a sound wave would. These cells will be grown in a dish with spiral ganglion neurons so that they can be observed using a microscope.
The cells will be grown together for several days to allow them to form new synapses. After this time, they will assess the activity of the synapses by measuring the response of the spiral ganglion neurons to activation of the inner hair cells by light. They will also investigate the ability of specific chemicals or drugs to improve how well these newly-formed synapses work.
Benefit
This research seeks to develop and provide tools that will help the research community to develop drugs that can improve or restore hearing after hearing loss. It could ultimately lead to new treatments that can regenerate inner hair cell synapses.