Award details

The function of the commissure of the inferior colliculus in auditory processing

Reference	BB/J008680/1
Principal Investigator / Supervisor	Professor Adrian Rees
Co-Investigators / Co-Supervisors
Institution	Newcastle University
Department	Institute of Neuroscience
Funding type	Research
Value (£)	365,768
Status	Completed
Type	Research Grant
Start date	01/10/2012
End date	31/05/2016
Duration	44 months

Abstract

This proposal addresses the important, but neglected, question in audition of why the left and right divisions of the brainstem auditory pathway are interconnected at the level of the inferior colliculi. These two nuclei are the principal midbrain centres of the auditory system and they receive converging input from several brainstem nuclei. They provide the main input to the auditory thalamus, and, thus indirectly, the cortex. Their second major output (via the commissure of the inferior colliculus) is to the other inferior colliculus - probably constituting its largest input from any single nucleus. We propose that these interconnections play an essential role in the analysis leading to the localisation and recognition sound. Specifically, we hypothesise that intercollicular comparison of activity operates to overcome the problem that neural activity in one colliculus is modulated by more than one sound parameter and therefore does not signal information unambiguously. This explanation is consistent with our understanding of how sounds are localised by the extraction of interaural differences in the timing and level of sounds at the ears. We seek evidence that supports this hypothesis in a guinea pig in vivo model by recording sound-evoked neural activity in one inferior colliculus while deactivating its counterpart on the other side. Reversible deactivation will be achieved principally by tissue cooling, with microdialysis of drugs providing an additional control. Electrophysiological recordings will encompass fine grain analysis from single unit recordings, using multiple electrodes to capture the relationship between neuronal responses and the topography of the structure, and neuronal population activity represented by local field potentials, and evoked potentials. We will test predictions about how one inferior colliculus influences responses in the other to sound frequency, level, interaural time differences, and interaural level differences.

Summary

Neural signals generated by the ears in response to sounds feed into two mirror image pathways on either side of the brainstem. While both left and right divisions receive inputs from both ears, the right side is dominated by information about sounds on the listener's left side and vice versa. This application proposes that the localisation and recognition of sound sources depend on the activity in one side being compared and referenced to the other. This interaction overcomes the problem that the outputs of neurons on one side alone are ambiguous because they don't respond exclusively to one attribute of sound, thus a change in a neuron's firing can reflect a change in the loudness of a sound, a shift in its position, or both. We propose that the large bundle of fibres interconnecting the two inferior colliculi (the auditory centres in the midbrain where the brainstem pathways culminate) provides the basis for mediating this left- right comparison. Since all signals reaching the higher cortical centres are processed en route within the inferior colliculi they are ideally situated to facilitate such an interaction. Furthermore, the bundle of fibres (the commissure) that connects one colliculus to the other is one of the largest inputs each inferior colliculus receives, and it terminates within the colliculus in a highly organised fashion. We seek to investigate the functional role of the commissural connections by temporally deactivating the inferior colliculus on one side of the brain and investigating what effect this has on the neural responses to sounds in the other inferior colliculus. We have developed and tested a means of rapidly deactivating the colliculus by cooling it. This is achieved by placing a small loop of stainless steel tubing on its surface through which we pump a coolant at subzero temperature. We can check that that the cooling effect is limited to the intended structure by measuring brain temperature with a tiny thermocouple, but asa double check, will also apply a method that enables us to infuse drugs that block neural activity into the inferior colliculus. We will also examine the effect of cutting the commissural fibres directly. The experiments will be performed in the anaesthetised guinea pig so that we can record the neural activity elicited by sounds. We will measure different aspects of brain activity, including the responses of single neurons (recorded simultaneously in different regions of the inferior colliculus), and electrical signals that represent the activity of large populations of neurons. By comparing these fine grain and summary responses to different types and combinations of sound stimuli before, during, and after deactivation of the other inferior colliculus we will discover how one inferior colliculus influences the other in different situations. We predict, that blocking commissural input will influence several facets of sound processing - a view supported by pilot studies. Specifically, we expect to observe changes in responses to features of sound that signal its location. Sounds in different locations give rise to differences in the level and timing of the sound between the ears. Recent discoveries about how the brain computes sound position from these differences suggest that referencing of left and right activity is important. We know little about the organisation of commissure of the inferior colliculus, and even less about its function in hearing. The outcomes of this research will, therefore, provide information of fundamental importance about the role of these connections in hearing, and help us better to understand the mechanisms of sound perception. The inferior colliculus is also being assessed for implanting an auditory- brain prosthesis to benefit patients who, through trauma or disease, have lost the nerves between the ears and the brain. Success in developing such a device depends on a greater understanding of the inferior colliculus.

Impact Summary

Private sector companies developing brain implants and prosthetic hearing devices: Through this impact the work contributes to Grand Challenge 3 - Fundamental bioscience enhancing lives and improving wellbeing (BBSRC Delivery Plan). Knowledge about the function of the brainstem pathways in auditory perception will benefit companies working towards the development of auditory brain implants to restore hearing. Currently these devices are implanted in the brainstem at the level of the cochlear nuclei, (~1100 implantations performed up to 2009). They offer limited restoration of function and work is afoot to develop a midbrain implant targeted at the inferior colliculus (IC). Progress depends on understanding the circuitry of the IC for the configuration of stimulating electrodes, and the development of the stimulation paradigms. A general understanding of brain mechanisms underlying auditory perception is also important in the development of hearing aid and cochlear implant technology. Such developments will lead to life enhancing technologies for those who suffer from hearing loss and economic benefits for the companies concerned. Private sector companies developing computer based sound recognition systems: The ability to recognise speech and other sounds in sound cluttered environments has long been a goal of researchers working on machine based analysis of sound. Biologically inspired systems have an important role to play in the development of such devices and the work will contribute to these studies by providing insight into a major component of auditory pathway and its role in hearing. Patients who are candidates for auditory brain implants and the clinicians treating them: The work will benefit the development of auditory prosthetic devices (see above) that have the potential to make a significant impact on the quality of life for patients with deafness caused by loss of the auditory nerves through the impact of brain trauma or disease such as neurofibromatosis type 2 - a condition with an incidence of ~1:40000. A consequence of the surgical removal of Schwannomas from the vestibular nerve is bilateral loss of the cochlear nerve leaving the patient totally deaf. Brain implants can restore some degree of hearing in these patients, and the IC, the focus of this research, is a target centre for such a device. Charities that promote hearing research and support hearing impaired people: The findings of the research will benefit charitable organisations such as RNID and Deafness Research UK. The work will benefit their efforts by stimulating further research projects, and through its impact on the development of prosthetic devices, will enable them to communicate exciting developments to potential beneficiaries and donors. Training of postdoctoral research assistants, postgraduate and undergraduate students maintaining transferable skills in in vivo neuroscience for economic benefit: The work uses sophisticated in vivo techniques in systems neuroscience, a speciality that has declined notably in the UK and internationally over the past twenty years. It is, however, an important mode of studying the brain and retention of these skills is important for maintaining capacity in the commercial bioscience sector as well as in academia. The project will offer training in this area to the postdoctoral researcher and to postgraduate students who would contribute to the project. Undergraduate students in biosciences will gain insight into in vivo experimentation via final year dissertations. Such experience and training will help maintain the pool of skilled in vivo researchers. The general public: The work will contribute to public engagement activities organised by the Institute of Neuroscience, including public lectures, activities at open days and science festivals. The public will benefit from a greater understanding auditory neuroscience and how it can impact on the alleviation of deafness.

Committee	Research Committee A (Animal disease, health and welfare)
Research Topics	Neuroscience and Behaviour
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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