The neural basis of perceptual sensitivity to sound in auditory cortex of the mouse.

Lead Research Organisation: Imperial College London
Department Name: Dept of Bioengineering

Abstract

The auditory world is noisy and full of distractions, but our brains are remarkably good at detecting, and extracting important sounds while ignoring the background. If a person mentions your name at the other end of a noisy room, it is quite likely that you will stop what you‘re doing, and listen to the speaker‘s words. As you do this, you lose awareness of the other noisy goings on around you. How the brain performs this amazing task is the subject of my research.

My goals are to determine:

- How the brain responds to important sounds when they occur in noisy environments.
- How the brain improves sound detection in noisy environments using the natural properties of sound.
- How the brain signals that it has heard an important sound.

To do this, I‘m going to present sounds to mice and record brain activity in auditory cortex, which is thought to be involved in higher-level processing of sound. I will train mice to perform a task where they must listen and indicate when they have heard a particular sound. I will explore whether their brain activity differs between occasions when indicate they have or have not heard the sound.

Technical Summary

The natural world consists of many separate and interfering sound sources. In animals, these sounds converge at the cochlea, which reports sound frequency to the brain. Somehow, the brain is able to separate and group frequency information into distinct auditory objects in order to build accurate perceptions of the world. The ability to detect salient sounds in the environment is critically important to the survival of many animal species, and is a key factor in human communication. Such sounds are often embedded within noisy backgrounds, reducing the signal-to-noise ratio at which the auditory system must operate, and making detection more difficult. The brain is known to exploit certain features of natural sounds in order to improve signal detection, but the mechanisms by which it performs these tasks remain largely unknown.



Therefore, the overall aim of this project is to understand how activity in auditory cortex influences signal perception in the presence of background noise. By modulating the amplitude of background noise coherently, it is possible to improve signal detection. This is a well-characterised psychoacoustic phenomenon called co-modulation masking release, the mechanism of which I shall investigate using electrophysiological recordings in the auditory cortex of anaesthetised and awake-behaving mice.



My key goals are:

1. To determine how modulations in background noise influence the representation of acoustic signals in auditory cortex.

2. To determine how the perceptual interpretation of a stimulus is influenced by auditory cortical activity.



First, using extracellular population recordings, I will establish how patterns of firing within populations of auditory cortical neurons are affected by noise modulations. Second, using whole cell recordings from single cells, I will determine the mechanisms that underlie these changes. Subsequently, mice will be trained to detect pure tones embedded in modulated background noise in a behavioural task. I will then record neuronal activity in auditory cortex whilst they perform this task, and therefore directly relate neuronal activity to perceptual outcome. Finally, I will determine whether single neuron stimulation in auditory cortex can influence task outcome.



Having characterised the mechanisms underlying signal detection in the brain, they may then be applied to improve synthetic listening devices: both cochlear implant technology for the hearing impaired, and other machine listening systems (e.g. for accurate speech recognition in noisy environments). Furthermore, by studying how complex sound information is processed in the auditory cortex, we may uncover fundamental principles about how neural networks perform sensory discriminations.

Publications

10 25 50
 
Description Quality Assurance in Animal Research
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Membership of a guidance committee
 
Description Intra-European Fellowship for Matthew Brown
Amount € 231,283 (EUR)
Funding ID PFC-DOPA 
Organisation Marie Sklodowska-Curie Actions 
Sector Charity/Non Profit
Country Global
Start 04/2013 
End 03/2015
 
Description Medical Research Foundation Small Equipment Grant
Amount £72,000 (GBP)
Organisation Medical Research Council (MRC) 
Department Medical Research Foundation
Sector Charity/Non Profit
Country United Kingdom
Start 04/2014 
End 10/2014
 
Description Research Grant - Open Call
Amount £407,502 (GBP)
Funding ID PSA678_BMPF 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2016 
End 03/2019
 
Description Royal Society Research Grant
Amount £14,950 (GBP)
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 12/2011 
End 12/2012
 
Description Wellcome Trust Investigator in Science
Amount £1,498,083 (GBP)
Funding ID 209453/Z/17/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2018 
End 04/2023
 
Description Young Investigator Award
Amount $330,000 (USD)
Funding ID RG0089 
Organisation Human Frontier Science Program (HFSP) 
Sector Charity/Non Profit
Country France
Start 09/2012 
End 08/2016
 
Title Trace-3D 
Description An (almost) user-free algorithm written in Matlab, that precisely localizes neurites across cortical layers in 3-D data sets. 
Type Of Material Computer model/algorithm 
Year Produced 2018 
Provided To Others? Yes  
Impact This approach has allowed us to analyse data that would otherwise be too noisy/complex to handle otherwise. The results were published in a paper Song et al, 2018 Cell Reports 
URL https://github.com/iocalangiu/trace-3d
 
Description High-resolution mapping of age-related functional changes in cortical connectivity 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution In vivo whole cell recording from aged animals
Collaborator Contribution In vitro whole cell recording from aged animals
Impact EPSRC-funded PhD studentship
Start Year 2014
 
Description In vivo multiphoton-targeted robotic patch clamp 
Organisation Imperial College London
Department Department of Life Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Providing expertise and calibration data for construction of patch clamp robot
Collaborator Contribution Designing and programming robot
Impact Abstract submitted to 2013 Society for Neuroscience meeting, San Diego USA
Start Year 2013
 
Description Investigating mechanistic basis of working memory in the prefrontal cortex of mice 
Organisation Champalimaud Foundation
Department Champalimaud Centre for the Unknown
Country Portugal 
Sector Academic/University 
PI Contribution We have met several times and devised a multidisciplinary collaboration to explore the brain circuits that encode working memory. Together with our collaborators, we have jointly applied for a Human Frontiers Science Program Young Investigator grant. Our initial application was shortlised, and we submitted a full application in September 2011. As part of the application, our lab has collected new data (intracellular recordings from anatomically identified neurons in prefrontal cortex) that were incorporated into the full submission. A completed grant submission was the equal effort of all three research groups.
Impact Invited full grant submission to Human Frontier Program. Final decision in Feb 2012. Collaboration is multidisciplinary - Portugal: theoretical modelling; Korea: optogenetics
Start Year 2010
 
Description Investigating mechanistic basis of working memory in the prefrontal cortex of mice 
Organisation Korea Advanced Institute of Science and Technology (KAIST)
Department Center for Functional Connectomics
Country Korea, Republic of 
Sector Academic/University 
PI Contribution We have met several times and devised a multidisciplinary collaboration to explore the brain circuits that encode working memory. Together with our collaborators, we have jointly applied for a Human Frontiers Science Program Young Investigator grant. Our initial application was shortlised, and we submitted a full application in September 2011. As part of the application, our lab has collected new data (intracellular recordings from anatomically identified neurons in prefrontal cortex) that were incorporated into the full submission. A completed grant submission was the equal effort of all three research groups.
Impact Invited full grant submission to Human Frontier Program. Final decision in Feb 2012. Collaboration is multidisciplinary - Portugal: theoretical modelling; Korea: optogenetics
Start Year 2010
 
Description Role of cerebellum in active whisking 
Organisation Duke-NUS Graduate Medical School
Country Singapore 
Sector Academic/University 
PI Contribution Joint supervision of a PhD student; in vivo recordings from cerebellum in my lab
Collaborator Contribution Joint supervision of a PhD student; in vitro recordings from cerebellum in my lab; provision of a technology (GM mouse strain)
Impact None as yet
Start Year 2012
 
Description The representation of complex sounds by neural populations in the auditory cortex 
Organisation Imperial College London
Department Department of Bioengineering
Country United Kingdom 
Sector Academic/University 
PI Contribution We have secured links with an industrial partner to provide equipment and support to establish a 2-photon imaging system in the department. The partner will provide loan of the kit for a 2-photon microscope (in return for use of the machine 1 day a week). With this support, my collaborator and I have secured funding from across the College (£45000 in total), to purchase a high spec laser for the task of 2-photon excitation/imaging.
Impact Outcomes: industrial partnership (formal agreement pending) Cross-faculty funding (secured) Collaboration is not multi-disciplinary
Start Year 2011
 
Description xperimental and computational study of auditory receptive field properties and connectivity 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Experimental measurement and perturbation of auditory receptive fields
Collaborator Contribution Computational modelling
Impact EPSRC-funded PhD studentship has been awarded
Start Year 2014
 
Description Panel Member (London 2013) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Symposium on 'Future of Future Expertise' - organised by the Victoria and Albert Musuem. Multidiscplinary panels from across the arts and sciences. Panel members gave talks about the future of their fields and took questions. The day was recorded for a audio podcast to be released at a later date.

None as yet
Year(s) Of Engagement Activity 2013