Cochlear Type II Neurons In Contralateral Suppression
Funder
National Health and Medical Research Council
Funding Amount
$459,434.00
Summary
Sound in one ear affects hearing in the other ear. This contralateral suppression is important for hearing attention and protection from noise damage. We will test the hypothesis that cochlear type II sensory neurons provide the sensory input for this process using models where neuronal development is altered, or the neurons are removed. The study addresses hearing disability in society, facilitating cochlear prosthesis development and the understanding of hearing loss.
Hearing Protection Conferred By P2X2 Receptor Signaling In The Cochlea
Funder
National Health and Medical Research Council
Funding Amount
$580,019.00
Summary
Hearing loss from noise damage and ageing is the principal sensory disability in our society. This project will determine the contribution of the P2X2 receptor to protection from noise-induced hearing loss. We have found that P2X2 knockout mice have minimal temporary threshold shift. We will investigate the physiological basis for this and determine why this mouse model has greater hearing loss with intense sound and faster age-related hearing loss compared with wildtype controls.
Inner Ear Protein Function Studied Using RNA Interference
Funder
National Health and Medical Research Council
Funding Amount
$365,230.00
Summary
The proper functioning of all cells tissues and organs depends on specific proteins that are manufactured by readout from the genome. The inner ear is no exception to this general principle and hence the normal hearing process depends critically on the proper functioning of key proteins. However, because of inherent limitations in the methods used to study their function in living tissues, the precise role of many inner ear proteins in the complex hearing process is not known or is at best poorl ....The proper functioning of all cells tissues and organs depends on specific proteins that are manufactured by readout from the genome. The inner ear is no exception to this general principle and hence the normal hearing process depends critically on the proper functioning of key proteins. However, because of inherent limitations in the methods used to study their function in living tissues, the precise role of many inner ear proteins in the complex hearing process is not known or is at best poorly understood. In this project we will use a recently developed technique called RNA interference, to reduce the amounts of specific targeted proteins in the inner ear of experimental animals. We will then study the effects on the inner ear's ability to detect sounds. The technique differs from other genome-manipulating methods because it can be applied to a single intact organ in the mature animal. The results of this project will illuminate the role of specific inner ear proteins in the process of sound detection. The project will also demonstrate the feasibility of using the RNA interference technique to modify function in the adult inner ear, thus paving the way for future therapies for inherited hearing disorders.Read moreRead less
Intrinsic Hearing Protection Mechanisms: A Pathway To Prevention Of Noise-induced Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$625,900.00
Summary
Noise-induced hearing loss (NIHL) is a significant contributor to the total burden of disease. We recently determined that when the ear is exposed to sustained noise, the cochlea is protected from damage by activation of a specific (P2X2) receptor, evident as reversible hearing adaptation. This study will determine the downstream signalling from this receptor. This will support assessment of vulnerability to NIHL and contribute to development of hearing therapeutics.
Physiological significance of transient receptor potential (TRPC3) ion channels in the cochlea. The project seeks to discover the function of transient receptor potential (TRPC3) ion channels in the cochlea. Recent studies have suggested that these proteins, which are expressed by the sensory and neural cells, are key elements regulating sound transduction and neurotransmission. The new knowledge about the physiological processes underlying hearing that this work will provide, will significantl ....Physiological significance of transient receptor potential (TRPC3) ion channels in the cochlea. The project seeks to discover the function of transient receptor potential (TRPC3) ion channels in the cochlea. Recent studies have suggested that these proteins, which are expressed by the sensory and neural cells, are key elements regulating sound transduction and neurotransmission. The new knowledge about the physiological processes underlying hearing that this work will provide, will significantly benefit national and international translational research that seeks to develop systems for controlling the sensitivity of our senses, developing biosensors, interacting with neural networks and developing neural prostheses. International collaborators in this project have enabled development of new models, technology and research training opportunities.Read moreRead less
The evolution of dim light vision in vertebrates. High sensitivity (rod-based) vision has been extremely important for the survival and adaptive radiation of many vertebrates, including humans over evolutionary time. This multidisciplinary project will reveal the evolutionary and physiological constraints on early photoreception and the difficulties in operating over an enormous range of lighting conditions. Not only will the findings be crucial for our understanding of basic mechanisms of dim l ....The evolution of dim light vision in vertebrates. High sensitivity (rod-based) vision has been extremely important for the survival and adaptive radiation of many vertebrates, including humans over evolutionary time. This multidisciplinary project will reveal the evolutionary and physiological constraints on early photoreception and the difficulties in operating over an enormous range of lighting conditions. Not only will the findings be crucial for our understanding of basic mechanisms of dim light vision, but also provide potential insights into the physiological bases of various rod dystrophies affecting humans and the improved design of more sensitive cameras and safe light environments for rearing animals in captivity e.g. for aquaculture.Read moreRead less
NEURAL MODULATION OF HEARING LOSSES INDUCED BY LOUD SOUND
Funder
National Health and Medical Research Council
Funding Amount
$290,500.00
Summary
Loud sounds, from occupational and recreational sources, are the most common threat to hearing and can result in temporary hearing losses (as might be experienced after an evening at a noisy pub or concert) or permanent hearing losses (after prolonged or multiple loud sounds, as for example in a noisy work environment). Noise reduction programs are either not always possible or effectively applied. A parallel strategy is the study of biological mechanisms that may ameliorate hearing damage, with ....Loud sounds, from occupational and recreational sources, are the most common threat to hearing and can result in temporary hearing losses (as might be experienced after an evening at a noisy pub or concert) or permanent hearing losses (after prolonged or multiple loud sounds, as for example in a noisy work environment). Noise reduction programs are either not always possible or effectively applied. A parallel strategy is the study of biological mechanisms that may ameliorate hearing damage, with a view to optimising such mechanisms. I propose to build on seminal Australian work to examine how one such system, nerves from the brain to the inner ear (the site of most damage from loud sounds), modulates hearing losses caused by loud sounds. Early studies indicated these nerves could protect from damage induced by short-lasting loud sound and this has led to international interest in functional applications of such protection to reduce hearing damage suffered by humans. However, my recent work indicates the nerves exert complex protective and exacerbative effects to loud sounds similar to common trauma or occurring under conditions similar to common trauma. They even exacerbate hearing losses due to loud sound, especially when there is an imbalance in hearing sensitivity in the two ears (bilateral) similar to what is common in humans. These findings make it critical that functional application be delayed until the full range of effects exerted by the nerves is understood. I propose to elucidate the novel complex effects of these nerves to loud sound. Specific aims are: (1) To understand effects of these pathways to loud sounds like those encountered by humans, (2) To investigate how chronic imbalanced bilateral hearing sensitivity, like that common in humans, alters effects of the nerves and when they change from being protective to exacerbative, (3) To adduce how an atraumatic sound affects hearing losses due to later loud sound and the role played by these nerves.Read moreRead less
Improving Music Appreciation For People With Prosthetic Hearing Devices By Enhancing Auditory Stream Segregation
Funder
National Health and Medical Research Council
Funding Amount
$266,560.00
Summary
Music perception is one of the most often-cited problems for people with hearing aids or cochlear implants. Part of the problem is related to the reduced ability to hear different instruments or melodic lines separately. This ability is based on perceptual differences between auditory streams. Psychophysics experiments will be performed to understand the effect of different acoustic parameters on auditory streaming. An innovative approach to restore music appreciation will be tested on people wi ....Music perception is one of the most often-cited problems for people with hearing aids or cochlear implants. Part of the problem is related to the reduced ability to hear different instruments or melodic lines separately. This ability is based on perceptual differences between auditory streams. Psychophysics experiments will be performed to understand the effect of different acoustic parameters on auditory streaming. An innovative approach to restore music appreciation will be tested on people with impaired hearing.Read moreRead less
Neurosteroid Modulation Of GABA-inhibition In Vivo: Central Auditory Pathway Models
Funder
National Health and Medical Research Council
Funding Amount
$331,650.00
Summary
All neurons at higher levels of the central nervous system signal in response to the outcome of various excitatory and inhibitory inputs (synapses) from other neurons. Most of the fast-acting inhibition is mediated by chloride ion influx through a channel which is gated by the neurotransmitter GABA. Termed the GABAa-receptor, this channel is known to be modulated by a wide range of pharmacological agents (e.g. valium; ethanol, many anaesthetics) which may enhance or suppress its efficacy. There ....All neurons at higher levels of the central nervous system signal in response to the outcome of various excitatory and inhibitory inputs (synapses) from other neurons. Most of the fast-acting inhibition is mediated by chloride ion influx through a channel which is gated by the neurotransmitter GABA. Termed the GABAa-receptor, this channel is known to be modulated by a wide range of pharmacological agents (e.g. valium; ethanol, many anaesthetics) which may enhance or suppress its efficacy. There are also good reasons for concluding that there is a capacity for modulation by endogenous substances. Brain synthesized steroids (neurosteroids) are known to have a potent enhancement effect upon the efficacy of GABAa-receptors, and have been implicated in a number of clinical situations, including menstrual cycle related depression. Work of others has shown that rapid synthesis of neurosteroids acts to increase inhibition in response to anxiety-inducing stimuli. Our recent work has shown that neurosteroids mediate an induced increase in inhibition in the auditory midbrain area. A surprising aspect of that study was that neurosteroids also appear to mediate ongoing levels of inhibition. This now allows us to use the many inhibitory interactions in the auditory pathway as potential models for studying the role of neurosteroid modulation of GABA inhibition in normal brain function. This is important because a number of medical treaments have the side effect of changing the synthesis of neurosteroids. We will also use an auditory system model of neurotrauma to examine the role of neurosteroids in increasing inhibition (to counter a potentially lethal increase in excitability). The work will involve electophysiological functional measurements and the development of highly sensitivity analytical protocols using an electrospray mass spectrometer for direct measurement of neurosteroids in submicrogram samples of brain tissue.Read moreRead less
Suction pipette measurements of mammalian rod photoreceptor recovery following intense bleaching exposures. The aim of this project is to discover the events and processes that prevent retinal photoreceptors from recovering instantaneously following the cessation of exposure to extremely bright illumination. Recordings will be made from single rod photoreceptors cells isolated from the mammalian retina. The work will uncover the relative roles of the 'photoproducts' created when rhodopsin abso ....Suction pipette measurements of mammalian rod photoreceptor recovery following intense bleaching exposures. The aim of this project is to discover the events and processes that prevent retinal photoreceptors from recovering instantaneously following the cessation of exposure to extremely bright illumination. Recordings will be made from single rod photoreceptors cells isolated from the mammalian retina. The work will uncover the relative roles of the 'photoproducts' created when rhodopsin absorbs light: e.g. intermediates such as metarhodopsin and opsin. The molecular knowledge obtained will help us to understand why it is that the visual system recovers so slowly after the eye has experienced very intense light.Read moreRead less