Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - LISTEN (Liaison in Scientific Training for European auditory Neuroscience)

Teaser

Hearing loss is a rapidly expanding health concern, which has a devastating social impact, reducing our ability to have a conversation in noisy environments, and consigning the deaf to social isolation. Hearing loss can have other debilitating consequences, as sufferers begin...

Summary

Hearing loss is a rapidly expanding health concern, which has a devastating social impact, reducing our ability to have a conversation in noisy environments, and consigning the deaf to social isolation. Hearing loss can have other debilitating consequences, as sufferers begin to hear phantom sounds; these are loud, distracting and imaginary sounds, known as tinnitus. Although tinnitus is typically preceded by hearing loss, it is usually not generated in the ear, but is ‘created’ by the brain. The general consensus is that tinnitus results from abnormal excitability in the central auditory system, but neither the location of the problem nor the exact plasticity processes underlying tinnitus are well understood. Consequently, there are few tinnitus treatments beyond management of symptoms.
Hearing loss and tinnitus are large medical problems that require a multidisciplinary approach aimed at understanding the underlying mechanisms.
The LISTEN (Liaison In Scientific Training for European auditory Neuroscience) training network consists of European auditory neuroscientists working with several European companies to improve hearing aids (including cochlear implants) and pharmacological treatments for tinnitus and hearing loss. The LISTEN network has formed this liaison to train 10 Early Stage Researchers (ESRs) in auditory neuroscience.
The overall objectives for LISTEN are:
1) To elucidate how the auditory system encodes complex sounds, both in normal and compromised hearing.
2) To study the underlying mechanisms of tinnitus, and test possible pharmacological treatments.
3) To train 10 ESRs to acquire technical skills and broader knowledge necessary in modern neuroscience research, while also learning to relate and translate their work for industrial and clinical applications.

Work performed

The first year of LISTEN has mostly been dedicated to recruitment of ESRs, which was finished before the end of month 12 with a team of 10 enthusiastic young researchers. After the first year meeting in month 11, including the first training event, year 2 has focused on LISTEN training and research.
Good progress has been made on both training and scientific progress. All beneficiaries have successfully started their research projects.
The first work package aims to elucidate how the auditory system encodes complex sounds, both in normal and compromised hearing. Examples of the progress during the first period are:
-To investigate how the inner ear encodes complex sounds a novel imaging technique called Optical Coherence Tomography (OCT) was established. This technique allows to study sound-induced movements in inner ear structures that were previously inaccessible. This technique allowed to define much better which structures in the inner ear are responsible for the decoding of complex sounds. A first publication of these results has come out in Nature Communications (Cooper et al, 2018).
-To better understand how complex sounds are encoded in the brain, recordings from different auditory and non-auditory regions were made. It was found that in the medial prefrontal cortex, some cells can encode novelty sounds, i.e. sounds that had not been played in the recent history. These findings will allow a study of the cellular mechanisms that allow to discriminate changes in the environment.
The second work package aims to study the underlying mechanisms of tinnitus, and test possible pharmacological treatments. Examples of the progress during the first period are:
-Several mouse models that showed relatively large responses to sound in the central auditory system, which is thought to be characteristic for the presence of tinnitus, were studied in detail, in order to better understand the underlying molecular and cellular changes. Differential responses within the different tests were found, suggesting the possibility to define the pathological impairment in more detail. The observed abnormal responses to complex sounds might be used to allow a more precise diagnosis of hearing impairments in humans.
-A better understanding of the underlying cause for a form of progressive hearing loss in humans was obtained by studying the inner ear of a mouse model for this disease. Since hearing loss is a main risk factor for tinnitus, this will allow to better define underlying mechanisms, and study the development of tinnitus in this mouse model.
-Progress was obtained to define in more detail the cellular mechanisms underlying tinnitus induced by high doses of salicylate, the active ingredient in aspirin. These results can be used as the basis for studying the cellular mechanisms underlying other forms of tinnitus, including those that follow hearing loss.
An important part of the first period of this ITN has been devoted to training. Apart from a five-week summer course on Auditory Neuroscience, a large number of workshops were organized to train the ESRs in a variety of techniques and topics, which included Viral technique, Eye blink conditioning, in vivo cell physiology and two-photon imaging, Evoked Potentials, Matlab, auditory genetics, experimental design and database management. Both annual meetings included trainings in transferable skills (management, communication). An important part of the training involved secondments, in which new techniques and methods were learned from other laboratories within the LISTEN consortium

Final results

In the first two years of the project, a major effort concerned the establishment of new measurement techniques, models for hearing loss or tinnitus, analyses techniques, etc. We expect that these methods will allow us to make progress according to the original plans and in some cases even go beyond the state of the art. A few examples of promising results that have been obtained:
-the establishment of a procedure to selectively ablate a selected set of auditory nerve fibers. This technique will allow to study the mechanisms underlying an inability to understand speech in noisy environments.
-the establishment of a technique that uses light to activate a defined set of auditory neurons in mice. This will allow to test to what extent optical stimulation can substitute for the auditory percept, leading to a better understanding of what an auditory percept constitutes and a possible new methods to directly activate the central auditory system.
-a task has been designed that allows to study whether attention changes how the location of where sounds come from is encoded in the auditory cortex.
-a new method was developed to change the activity of potassium channels by light in a mouse. Potassium channels are very important for controlling excitability in neurons, and changes in excitability are thought to underlie tinnitus. This method will thus allow to study the impact of potassium channels on excitability in a much more controlled way than by classical, pharmacological methods.
In conclusion, we expect that the effort put into training and establishment of techniques and research methods in the first years of the project will allow us to meet the original goals. For the remainder of the project, secondments will be very important for additional training and also for exposure to research in an industrial setting. For the socioeconomic impact, all ESRs will participate in outreach events. We expect that the research performed within the LISTEN project will contribute towards the understanding and management of hearing loss and tinnitus.

Website & more info

More info: http://www.listenscience.eu.