Deafness Research UK funds a record number of new projects.
Regulation of inner hair cell differentiation - controlling the production of auditory sensory hair cells.
Professor Matthew Holley, University of Sheffield, has been awarded £15,000 for a project to reveal the function of Gata3, a protein thought to govern the development, growth and survival of inner ear cells. Mutations in the gata3 gene lead to people developing similar symptoms to Hypoparathyroidism, Deafness and Renal anomaly (HDR) Syndrome.
This grant will allow Professor Holley to study the role of Gata3 in the development of the inner ear in collaboration with Professor Corfas from Boston. Gata3 and its downstream signalling pathway have been recognised as important targets for a number of diseases, notably cancer so tools and potential drugs have been developed by Pharmaceutical companies which can be applied to hearing research. As well as offering potential targets for future drug treatments of hearing loss, an understanding of the process of inner ear cell development is needed to ensure techniques such as stem cells can successfully replace damaged cells in the ear in the future.
Innervation of the hair cells of diminuendo mice mutants
This is a small grant of £15,000 awarded to Professor Carole Hackney, also based at the University of Sheffield. This study focuses on another recently identified type of mutation in microRNA which is responsible for some cases of hereditary deafness in man and in mice. This project is a collaboration between Biomedical Science department at Sheffield and the School of Life Sciences, Keele University and will take advantage of the expertise in detailed neuroimaging available at both institutions. Detailed analysis of what is happening during development of hearing in these mutant mice will give insights into the human condition and reveal potential targets for drug treatments of hearing impairment.
Analysis of auditory function and hair cell stereocilia in the plastin1 (Pls1) knock-out mouse
A small grant of £4,300 has been awarded to Dr Nico Daudet of the UCL Ear Institute to undertake this project. The funding will contribute towards consumable costs for 6 months to analyse the hearing loss in this new line of mice which develop hearing loss at an early age. Expertise available at the Ear Institute will enable the researchers to look in detail at the structure of the inner ear cells to try to identify what is going wrong. This pilot study could lead to the identification of a new animal model and candidate gene for hearing loss, which would be a crucial step towards better prognosis and treatment in humans.
Cell-type-specific neural activity in the auditory cortex of a tinnitus model
We are particularly pleased to be able to support a new researcher to the field of tinnitus. Dr Shuzo Sakata at the University of Strathclyde, has been awarded a grant of £14,748 that will enable him to set up a new laboratory studying the activity of neurons in a model of tinnitus using new, sophisticated electrophysiology techniques. The area of the brain called the auditory cortex is responsible for our perception of hearing and also for perceiving the phantom sounds that occur in tinnitus. The auditory cortex is very complex and made up of many different types of neurons. It may be that certain types are responsible for the phantom sounds and if identified may be targets for better treatments.
This grant will fund the purchase of specialised equipment to allow the researcher to measure the electrical activity of many neurons at once in specific regions of the auditory cortex of the brain in the tinnitus model, a technique called in vivo electrophysiology. Ultimately it is hoped that this type of research will lead to further understanding of brain activity in tinnitus patients and new targets for therapeutic interventions.
The effects of refractoriness on the neural response to pulse trains presented with a cochlear implant
Dr Ian Winter (University of Cambridge), will be utilising his small grant of £14,931 to take advantage of a visit of a leading researcher from the USA to the UK. Dr Steven Bierer, from the University of Washington, will be spending time in the Cambridge laboratory training the researchers in new techniques to study cochlear implants in a model, looking in particular at how the brain responds to electrical stimulation through the cochlear implant electrode.
Cochlear implants (CIs) have restored hearing to more than 100,000 deaf people world-wide. They do so by converting sounds picked up by a microphone worn behind the outer ear into trains of electrical impulses that are applied to an array of electrodes inside the inner ear and which stimulate the hearing- or auditory-nerve.
Although many CI patients understand speech well in quiet, even the most successful have problems in noisy backgrounds, and the perception of pitch is usually poor. Pitch perception is one of the most important auditory abilities. It plays a vital role not only in music appreciation and in the perception of the characteristics of speech, but is one of the main ways in which we separate competing sounds (such as voices) so as to process one of them. The poor pitch perception by users of cochlear implants constitutes perhaps the major limitation of these devices, and is the subject of substantial research and development by academic scientists and by manufacturers. The researchers at Cambridge believe that both a complete understanding of pitch perception, and successful attempts to improve it in clinical populations will require a firm understanding of its neural basis. They hope that this new project will lead to a better understanding of how pitch is perceived in our brains and improvements to cochlear implants to help users when listening in noisy situations and to music.
Mode-locked encoding of stimulus envelope throughout the cochlear nucleus
In a small grant awarded to Dr Christian Sumner at the MRC Institute of Hearing Research, Nottingham, funding of £13,120 will enable the researchers to further analyse an existing body of data consisting of recordings of brain activity in response to sound from a large number of volunteers. The researchers have recently developed new computer analysis techniques that can be applied to this data set to yield new information on how our brains process sounds.
Understanding how such sounds are represented in the brain is ultimately necessary if we are to understand how neural processing of speech is affected by hearing impairment, hearing aids and cochlear implants. The team at Nottingham have expertise in measuring the activity of auditory neurons in specific regions of the brain. This unique opportunity to access a large dataset of physiological data should increase our knowledge of the way in which the brain processes speech-like sounds and how hearing impairment affects this processing.
The function of different classes of inhibitory cells in the auditory cortex - an optogenetic approach
Small grant awards often allow researchers to retain key staff on a project before obtaining follow on funding or to obtain matched funding as is the case of the award made to Dr Jennifer Linden at the UCL Ear Institute. We have awarded her a small grant of £14,880 to fund a post doctoral researcher in her laboratory for 6 months and this has enabled them to obtain a further 6 months funding from the German Academic Exchange Service. This project will develop a new technique called optogenetics to study the function of particular types of neurons in the brain involved in hearing and look at what happens when hearing is lost.
The auditory cortex enables us to recognize complex sounds, such as the voice of a familiar person. It also plays an important role in directing attention to auditory objects, for example when we try to detect a particular sound in a noisy environment. While the majority of cells in the auditory cortex are excitatory neurons that receive and transmit sound information, about 20% of the neurons inhibit nearby cells. These cells are thought to be essential to auditory cortical function, and their dysfunction is associated with many common hearing deficits.
Progress in understanding inhibitory elements of the cortex has been slow because these cells form several distinct classes, which are difficult to distinguish using standard techniques. However, novel "optogenetic" techniques provide a way around this problem. The researchers propose to introduce light-sensitive proteins into genetically defined classes of inhibitory neurons in the mouse auditory cortex, so that they can identify these cells for analysis by shining light on the brains. The responses of these inhibitory neurons to sound can then be quantified and compared to those of nearby excitatory cells.