Physiological and histological investigation of structure and function of the normal auditory system

Lead Research Organisation: MRC Institute of Hearing Research

Abstract

This programme aims to improve our understanding of the function and connectivity of the auditory system. Sound waves in the air are transformed by the exquisitely sensitive structures of the ear into fluid movements that activate sensory hair cells in the inner ear (cochlea) then communicate them to the brain where they can be analysed.

Information is passed upwards from the cochlear nucleus, through a series of relay points, to the auditory cortex where sounds are consciously perceived. However, as well as this ascending path there is also an equally important descending path that modulates this ascending information dependent on context.

We will study the interactions between these pathways both at the relay points and in the cortex using complex stimuli such as animal vocalizations. We will also study the consequences of hearing loss in creating imbalance in the two pathways and in inducing tinnitus. We will use an animal model of tinnitus to study the mechanisms that lead to tinnitus and to evaluate drug therapies that may reduce the auditory aspects of tinnitus.

Technical Summary

The structure and function of the normal auditory nervous system is investigated in anaesthetised guinea pigs by a range of tract tracing, histological and neurophysiological methods. Results from this animal model direct our studies of post-mortem human brain tissue, one aim of which is to improve interpretation of human neuroimaging data from live subjects.

We investigate the processing and combination of information from the two ears both at the midbrain and cortical levels using electrophysiological recordings. This has enabled us to provide a detailed explanation of the mechanisms underlying the processing of localization cues and the way in which this may contribute to the segregation of spatially separate sound sources.

We study the morphology and response characteristics of single cells in the inferior colliculus and auditory cortex using a recording and labelling technique. This type of correlative data will allow a better understanding of the neural circuitry underlying the interaction between the multiple inputs to these auditory centres. We apply these techniques to the primary auditory cortex to investigate the processing that takes place within cortical columnar structures, which we also study in post-mortem human brains.

The auditory cortex is composed of two or three core areas surrounded by six or more belt areas. We investigate the function of these cortical areas using guinea pig con-specific vocalisations and have found that some areas appear to be specialised for analysing acoustic communication signals. We have also identified regions in the brain that will evoke con-specific communication calls when electrically stimulated. We combine this approach with recording of auditory cortex responses to external vocalizations to investigate the modulation of the neural representation of communication calls by self vocalizations.

We use histochemical methods to relate staining in the human auditory cortex to structural magnetic resonance images from the same (post-mortem) brains. This will allow us to identify core and belt areas in the human brain in human neuroimaging studies. Identification of the core and belt areas in the human is vital for interpreting normal neuroimaging data and in identifying abnormalities associated with clinical conditions.

We are developing a guinea pig model of tinnitus. Having used behavioural measures to identify animals that were experiencing tinnitus we have identified electrophysiological and histological markers that demonstrate the presence of tinnitus. We will use this model to test a variety of drugs, which when combined with acoustic enrichment, may lead to a rapid reversal of the tinnitus percept.

Finally, we are investigating the characteristics and the brain networks involved in tinnitus in humans. We do this combining audiological and questionnaire assessment with measuring brain activation using magnetoencephalography and functional magnetic resonance imaging. We have established that tinnitus sufferers exhibit altered brain oscillatory activity compared with appropriately matched controls.

Publications

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Alves-Pinto A (2010) Forward masking estimated by signal detection theory analysis of neuronal responses in primary auditory cortex. in Journal of the Association for Research in Otolaryngology : JARO

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Berger JI (2013) A novel behavioural approach to detecting tinnitus in the guinea pig. in Journal of neuroscience methods

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Berger JI (2015) Tinnitus-related changes in the inferior colliculus. in Frontiers in neurology

 
Description A glowing mention in Westminster Hall by our local MP
Geographic Reach National 
Policy Influence Type Citation in other policy documents
URL http://www.publications.parliament.uk/pa/cm201516/cmhansrd/cm150624/halltext/150624h0001.htm#1506245...
 
Description Centenary Awards
Amount £33,623 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 08/2012 
End 07/2013
 
Description International Project Grant
Amount £137,928 (GBP)
Funding ID G62 
Organisation Action on Hearing Loss 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2013 
End 07/2016
 
Description Small grant
Amount £1,120 (GBP)
Organisation British Tinnitus Association 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2012 
End 09/2012
 
Description Summer studentship
Amount £1,600 (GBP)
Organisation Action on Hearing Loss 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2015 
End 08/2015
 
Description Summer studentship
Amount £1,680 (GBP)
Organisation Action on Hearing Loss 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2010 
End 08/2010
 
Description Summer studentship
Amount £1,600 (GBP)
Organisation Action on Hearing Loss 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2014 
End 08/2014
 
Description Summer studentship
Amount £1,440 (GBP)
Organisation Action on Hearing Loss 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2010 
End 08/2010
 
Description Summer studentship
Amount £1,440 (GBP)
Organisation Action on Hearing Loss 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2012 
End 08/2012
 
Title Behavioural method for tinnitus in small animals 
Description Use of ear flick reflex to assess behavioural evidence of tinnitus in guinea pigs. 
Type Of Material Physiological assessment or outcome measure 
Provided To Others? No  
Impact Makes the guinea pig model of tinnitus more reliable and we are trying to adapt the method for use in humans. 
 
Description Cannabinoids in tinnitus 
Organisation University of Nottingham
Department School of Life Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution My research fellow, Ben Coomber, is engaged in a three year project to study the effect of cannabinoids as potential agents for ameliorating the symptoms of tinnitus in our guinea pig model.
Collaborator Contribution Staff such as Steve Alexander are international experts on the role of cannabinoids in the brain and the pharmacology of their receptors and second messenger systems.
Impact Successful application for funding to AOHL who provided a three year grant for the tinnitus project. The work involves three closely related neuroscience disciplines of physiology, pharmacology and psychology. This led to a paper on the effects of a cannabinoid agonist on tinnitus: BERGER, JOEL I., COOMBER, BEN, HILL, SAMANTHA, ALEXANDER, STEVE P. H., OWEN, WILLIAM, PALMER, ALAN R. and WALLACE, MARK N., 2017. Effects of the cannabinoid CB1 agonist ACEA on salicylate ototoxicity, hyperacusis and tinnitus in guinea pigs HEARING RESEARCH. 356, 51-62
Start Year 2013
 
Description Cross modal responses following cochlear implants 
Organisation National Institute for Health Research
Department NIHR Biomedical Research Unit, Nottingham University Hospitals NHS Trust
Country United Kingdom 
Sector Learned Society 
PI Contribution I am the leader for the sensorineural plasticity and rehabilitation strand of research. I provide advice and support with the neural imaging of cortical activity in hearing impaired children and co-supervise a PhD student who is working on an animal model of deafness with me.
Collaborator Contribution All the clinical interactions and cochlear implant work is performed by the clinical staff and they provide advice on the animal model.
Impact This is a multidisciplinary collaboration that should lead to a more accurate prognosis for children who are being considered for a cochlear implant. It involves interactions between an ENT surgeon a physiologist and neuroscientists.
Start Year 2011
 
Description Guinea pig communication 
Organisation Northeast Ohio Medical University
Department Department of Anatomy and Neurobiology
Country United States 
Sector Academic/University 
PI Contribution Collection and analysis of calls and the responses of cortical neurones to these calls.
Collaborator Contribution Help with analysis of calls and responses.
Impact Paper in Frontiers in Systems Neuroscience (2013); Paper in PLOS ONE (in press) 2018
Start Year 2011
 
Description Interaural time delays 
Organisation Ben-Gurion University of the Negev
Country Israel 
Sector Academic/University 
PI Contribution We collected data from brain recordings following acoustic stimulation.
Collaborator Contribution They provided detailed mathematical analysis of data we had collected.
Impact Zohar et al. (2011) paper in Journal of Neuroscience; Zohar et al. (2013) paper in PLoS one. Neurophysiology
Start Year 2009
 
Description Processing sound in the inferior colliculus 
Organisation Newcastle University
Department Institute of Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution Collection and analysis of responses to sound by over 2000 neurones in the guinea pig inferior colliculus.
Collaborator Contribution Help with analysis and interpretation.
Impact Paper in Journal of Physiology entitled, "Classification of frequency response areas in the inferior colliculus reveals continua not discrete classes"
Start Year 2012
 
Description Stimulus-specific adaptation 
Organisation University of Salamanca
Department Institute of Neuroscience of Castilla y Leon
Country Spain 
Sector Academic/University 
PI Contribution Professional advice and help with analysis and presentation of data.
Collaborator Contribution The experimental work with the collection and analysis of data was all done in Salamanca.
Impact A manuscript has been submitted but has not yet been published.
Start Year 2012
 
Description Thallium uptake in the brain 
Organisation Leibniz Association
Department Leibniz Institute for Neurobiology
Country Germany 
Sector Academic/University 
PI Contribution We used this technique in the guinea pig brain.
Collaborator Contribution They showed us how to load thallium salts into the brain and then demonstrate them histologically.
Impact Paper by Coomber et al. (2011) in Frontiers in Systems Neuroscience. Anatomy and physiology
Start Year 2009
 
Description Advisory Panels 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Providing expert advice on applications for grant support from these organizations

Funding of good quality research from the charity sector
Year(s) Of Engagement Activity 2010
 
Description Invited oral presentations 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact Invited lectures to health professionals at Institute of Acoustics

Providing a deeper understanding of the basic science underpinning management of hearing loss and tinnitus.
Year(s) Of Engagement Activity 2010
 
Description Public lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Highlighted some of the work going on in the Institute here and world wide.

Generated questions about cochlear implants and prosthetic devices for hearing
Year(s) Of Engagement Activity 2012
 
Description Teaching on Tinnitus 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Health professionals
Results and Impact Providing a basic science underpinning for a course on the management of tinnitus.

Increased awareness and further information for health professionals
Year(s) Of Engagement Activity 2009,2010
 
Description Visit by local MP 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact We hosted a visit by our local MP with lots of impressive demonstrations by our staff. A direct result was a glowing reference to our research in a subsequent Westminster Hall debate on 24th June 2015
Year(s) Of Engagement Activity 2015