Synaptic Transmission In The Mammalian Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$460,500.00
Summary
In order to properly understand the complex functions of the brain and the abnormalities underlying neurological disorders, we must understand how individual neurons communicate with each other. Communication occurs at specialized contacts, or synapses. An individual neuron may receive tens of thousands of synaptic contacts from hundreds or thousands of other neurons. Despite intensive investigation, the processes which regulate synaptic strength between central neurons are poorly understood. Th ....In order to properly understand the complex functions of the brain and the abnormalities underlying neurological disorders, we must understand how individual neurons communicate with each other. Communication occurs at specialized contacts, or synapses. An individual neuron may receive tens of thousands of synaptic contacts from hundreds or thousands of other neurons. Despite intensive investigation, the processes which regulate synaptic strength between central neurons are poorly understood. The overall aim of this proposal is to understand the basic mechanisms underlying synaptic transmission at excitatory and inhibitory synaptic connections in the mammalian brain. We will investigate specific synaptic connections in the central pathways of the auditory system, because our previous studies have demonstrated a number of key technical advantages in studying these synapses. We will use electrophysiological recording from synaptic terminals and neurons in isolated living slices of the brainstem of mice. We will use imaging techniques and electron-microscopy to examine the structural details of synaptic connections, as structure is thought to play a major role in determining the strength of synaptic transmission. We will also study the structural and functional properties of auditory synaptic connections in congenitally deaf animals. Our recent study comparing normal and congenitally deaf mice has already revealed significant differences. Our results will provide important insights in the regulation of synaptic strength in the central nervous system, and into the regulation of synaptic transmission at central synapses which have developed under conditions of abnormal sensory activation.Read moreRead less
The key to how the brain works lies in its capacity to modify the strength of its connections. During development, input to the brain from our sensory organs shapes the properties of synaptic contacts and target neurons. This project is aimed at understanding the pathways in the brain related to our sense of hearing, and discovering what is different about these pathways in congenital deafness, where the brain does not receive the appropriate signals during development.
Functional Characterisation Of Pendrin: The Anion Transporter Causing Pendred Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Mutations in the human pendrin protein cause progressive hearing loss from an early age in Pendred syndrome. Using techniques of molecular and cellular biology, we intend to test the effects of Pendred-causing mutations on the function of pendrin expressed in frog and cultured mammalian cells. Our approach will enable us to determine how pendrin functions in both the normal and diseased states, which is currently unknown. This will allow us to consider ways of correcting the ion channel defect a ....Mutations in the human pendrin protein cause progressive hearing loss from an early age in Pendred syndrome. Using techniques of molecular and cellular biology, we intend to test the effects of Pendred-causing mutations on the function of pendrin expressed in frog and cultured mammalian cells. Our approach will enable us to determine how pendrin functions in both the normal and diseased states, which is currently unknown. This will allow us to consider ways of correcting the ion channel defect associated with the Pendred syndrome.Read moreRead less
In the normal process of hearing, the brain actively selects sounds of interest from competing background sounds. This normal auditory function is indispensible for children and adults to cope in non-optimal listening environments, however the mechanisms by which such performance is achieved are poorly understood. This project will investigate the nerve circuits that enable this to occur and will also investigate how these circuits malfunction in various types of partial deafness. The results wi ....In the normal process of hearing, the brain actively selects sounds of interest from competing background sounds. This normal auditory function is indispensible for children and adults to cope in non-optimal listening environments, however the mechanisms by which such performance is achieved are poorly understood. This project will investigate the nerve circuits that enable this to occur and will also investigate how these circuits malfunction in various types of partial deafness. The results will improve our understanding of how we detect sounds and the impact of hearing pathologies on this process.Read moreRead less
Long-term Surgical And Socioeconomic Outcomes Following Aortopulmonary Septal Defect Repair In Children
Funder
National Health and Medical Research Council
Funding Amount
$89,197.00
Summary
About 2% of heart defects are due to communication between the 2 main arteries exiting the heart (truncus arteriosus and aortopulmonary window). If untreated, up to 30% of children die in the first year of life. With surgery many patients are now surviving into adulthood. The long-term outcomes are unknown. This study will review all patients with this defect across Australian and New Zealand. Results from this study will allow us to best manage these patients in the short and long-term.
Nerve pathways exist that carry information from the highest parts of the brain to the peripheral hearing organ, the inner ear. These descending control pathways have the potential to affect the hearing process in a number of ways; protecting from loud sounds, improving the detection of signals in noisy backgrounds, selecting stimuli of interest and regulating a variety of aspects of inner ear function. Abnormal function of these pathways can affect hearing sensitivity and may be important in ph ....Nerve pathways exist that carry information from the highest parts of the brain to the peripheral hearing organ, the inner ear. These descending control pathways have the potential to affect the hearing process in a number of ways; protecting from loud sounds, improving the detection of signals in noisy backgrounds, selecting stimuli of interest and regulating a variety of aspects of inner ear function. Abnormal function of these pathways can affect hearing sensitivity and may be important in phenomena such as tinnitus and other disorders of hearing. This project will investigate the subtle effects that selective activation of these pathways has on inner ear function and will attempt to unravel the different influences that subcomponents of the pathways have on the different aspects of hearing.Read moreRead less
Most adults will have already sustained damage to the tiny connections between hearing cells and nerve cells; a missing link in their auditory pathway. There is no way to repair the damage and our hearing will worsen over time. We now have compelling evidence that a growth factor therapy to the inner ear restores the connections. We will deliver world-first data to justify and set the parameters for a clinical trial for a therapy to treat hearing loss for the first time.
Improving Speech Perception Outcomes In Deaf Adults And Children Using Cochlear Implants
Funder
National Health and Medical Research Council
Funding Amount
$160,604.00
Summary
This project aims to further improve on speech understanding by deaf adults and children using the cochlear implant. In particular, we aim to individually modify the speech coding scheme on the basis of the basic hearing skills of the subject. In this manner, more speech information should be available and the users will likely gain more benefit from their cochlear implants. The speech processing strategy of the multiple-electrode cochlear implant, manufactured by the Australian biomedical compa ....This project aims to further improve on speech understanding by deaf adults and children using the cochlear implant. In particular, we aim to individually modify the speech coding scheme on the basis of the basic hearing skills of the subject. In this manner, more speech information should be available and the users will likely gain more benefit from their cochlear implants. The speech processing strategy of the multiple-electrode cochlear implant, manufactured by the Australian biomedical company Cochlear Limited, codes acoustic frequency information on electrodes which are located in the cochlea. The assignment of frequencies to electrodes is consistent with the ordering of pitch in the cochlea. For optimum performance, all electrodes would need to be perceptually distinct from each other. Recent research with adults and children has shown that this is not the case for a number of subjects as adjacent electrodes sound the same. Thus important speech information may not be heard by these subjects. In this project, we will determine how well adults and children are able to hear differences between the electrodes, and then provide speech processing schemes which exclude those electrodes which sound the same as others in close proximity. The project will compare these modified strategies with the standard strategy currently used by the subjects over time, so that any differences in the way adults and children are able to improve on speech understanding will be determined. As far as can be determined, this project will be the first investigation to improve on speech understanding in children using the cochlear implant.Read moreRead less