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

Lead Research Organisation: University of Nottingham

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

(around 400 words – max. 3,500 characters including spaces) 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.
 
Description Translational research in Hearing
Amount £289,838 (GBP)
Organisation Action on Hearing Loss 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2020 
End 04/2023