A decade ago the adult brain was thought of as a structurally-fixed organ. Against this are well-documented cases of slow recovery after massive injuries or stroke. Simple models of brain injury using the tactile, visual and auditory systems of animals as models have now revealed multiple stages of recovery (plasticity). Some of these are inbuilt into the wiring of the neural systems such that functional plasticity can result without the need for any structural or cellular changes. A second grou ....A decade ago the adult brain was thought of as a structurally-fixed organ. Against this are well-documented cases of slow recovery after massive injuries or stroke. Simple models of brain injury using the tactile, visual and auditory systems of animals as models have now revealed multiple stages of recovery (plasticity). Some of these are inbuilt into the wiring of the neural systems such that functional plasticity can result without the need for any structural or cellular changes. A second group of plastic phenomena depend upon minute changes in the connections between neurons and these are invoked in the first few days following an injury (synaptic plasticity; changes in the pattern and strength of the connections between neurons). Aside from being model systems, there are also parallels of this plasticity with clinical situations such as losses in hearing and sight, and of the adaptations made by the brain in response to prosthetics (e.g. bionic ear) and resorative surgery but the degree of relevance for these situations is unclear. An intriguing aspect of the experiments on auditory and visual systems is that neurons with inputs from both ears, or both eyes, undergo the plastic changes when the relevant sense organ on only one side is damaged but the other is intact. In fact, on the basis of the limited available evidence, it appears that the changes are independent of there being a normal input from the other side. This is difficult to explain in terms of the modern understanding neuronal plasticity at a cellular level. It is thus proposed to study both auditory and visual models of this brain plasticity with stimuli which are systematically varied to extract the extent of bilateral interaction in the induced plasticity. This will enable prediction of how these plasticity mechanisms will be involved in adaptations made to prosthetics and surgical corrections.Read moreRead less
Combining input from vision and hearing greatly enhances perception when information from one of these senses is degraded or incomplete, such as when tracking objects in foggy, dark or noisy places. This enhancement is of considerable importance because degraded input is the daily situation faced by many people with hearing or vision impairment. We will study the neural processes underlying our ability to combine vision and hearing to create a more reliable and accurate perception of the world.
Thalamic And Basal Forebrain Contributions To Auditory Cortical Reorganization Produced By Partial Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$364,768.00
Summary
When part of the cochlea is damaged in adult animals, leading to a partial hearing loss, the auditory area of the cerebral cortex reorganizes itself, so that the area deprived of input by the peripheral lesion is not silent, but is occupied by expanded representations of adjacent frequencies. This reorganization has been observed in a number of species, including non-human primates, and it seems likely that it also occurs in humans with cochlear damage and hearing loss of this sort. If it does, ....When part of the cochlea is damaged in adult animals, leading to a partial hearing loss, the auditory area of the cerebral cortex reorganizes itself, so that the area deprived of input by the peripheral lesion is not silent, but is occupied by expanded representations of adjacent frequencies. This reorganization has been observed in a number of species, including non-human primates, and it seems likely that it also occurs in humans with cochlear damage and hearing loss of this sort. If it does, it would have important consequences for the way in which input from a hearing aid or cochlear prosthesis (bionic ear) is processed in the brain. This Project is designed to clarify the nature of the systems in the brain that contribute to this form of cortical plasticity, using an animal model. One aim is to determine whether the plasticity is intrinsic to the cortex or occurs in the pathways over which information is conveyed to the cortex. This will be assessed by determining whether such plasticity is also found in the auditory thalamus, the final subcortical auditory nucleus from which information is sent to the cortex. The second aim is to determine whether the occurrence of plasticity is controlled by modulatory influences from the basal part of the forebrain. Neurons in this area project to many parts of the cortex, and evidence from other sensory systems suggests that these projections exert a permissive function, allowing the cortex to reorganize when input is altered. This aim will be pursued by determining whether cortical reorganization occurs after hearing loss when this basal forebrain system is inactivated. The significance of these studies is that they will elucidate the way in which the brain reorganizes itself when it is confronted with altered input. This information is important for our understanding of normal auditory information processing mechanisms and of the way in which input from prosthetic devices is processed in the hearing-impaired.Read moreRead less
One of the main trends in the evolution of the primate brain was the huge expansion of the cortical areas devoted to visual processing. However, the exact role of individual areas remains highly controversial, making detailed physiological and anatomical studies in suitable primate models a key step to elucidating their function in the human brain. We will address one particular aspect of this problem, namely the organisation of the cortical areas that provide visual control for skilled movement ....One of the main trends in the evolution of the primate brain was the huge expansion of the cortical areas devoted to visual processing. However, the exact role of individual areas remains highly controversial, making detailed physiological and anatomical studies in suitable primate models a key step to elucidating their function in the human brain. We will address one particular aspect of this problem, namely the organisation of the cortical areas that provide visual control for skilled movements. It is proposed that there are two parallel brain circuits involved in the analysis of motion, one tracking the movement of objects, and the other analysing a person s self-motion. Consider, for example, the task of a tennis player who has to return a serve. In order to achieve this, the brain must precisely integrate information about the ball s motion, as well as information about the player s speed and direction. This requires precise control of eye movements (to keep the eyes on the ball), as well as the ability to control the limb and trunk muscles. The aim of this study will be to map the anatomical framework underlying our ability to process all the relevant visual motion information, and to coordinate the appropriate motor responses. Such work is fundamental for understanding the functional organisation of the brain. It also has the potential to lay the groundwork for developments in areas of applied research, including medicine (e.g. the design of better rehabilitation strategies for people with brain damage), robotics- artificial intelligence (e.g. the improvement of artificial systems capable of vision), and the cognitive sciences (e.g. a better understanding of factors that limit human responses to visual stimuli).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
Temporal Processing In The Superior Olivary Complex: Impact Of Deafness And Peripheral Electrical Stimulation Strategies
Funder
National Health and Medical Research Council
Funding Amount
$225,500.00
Summary
The brain can use timing or temporal information to extract the frequency and location of sound. Timing information is coded by the pattern of responses of brain cells that match the period of the sound wave. These responses can be measured as small voltage spikes or action potentials. Integration of these responses from one brain-processing site to another relies on precise (temporally matched) firing among a population of cells that are activated in response to sound. Sound localisation relies ....The brain can use timing or temporal information to extract the frequency and location of sound. Timing information is coded by the pattern of responses of brain cells that match the period of the sound wave. These responses can be measured as small voltage spikes or action potentials. Integration of these responses from one brain-processing site to another relies on precise (temporally matched) firing among a population of cells that are activated in response to sound. Sound localisation relies on this temporal integration from information coming from both ears. Specifically, the integration of this information relies on the balance of incoming inputs from both ears, which maintains an appropriate time window depending on the location of sound in space. Recent evidence suggests that in deafness this process of integration is disrupted which may be possibly due to an inability to regulate the coherent activation of cells. This has implications for cochlear implant users whose ability to process temporal information is compromised by a loss of temporal coding ability resulting from prior deafness. In this project we will measure voltage changes occurring inside cells of the superior olivary complex, which contains a group of structures that integrate input from both ears. We will examine the ability of these cells to process temporal information in normal and deafened conditions. This study will lead not only to an understanding of basic mechanisms for auditory coding but also to improved electrical stimulation strategies for patients with cochlear implants.Read moreRead less
The Signals Of Nerve Cells That Provide The Capacity For Sight
Funder
National Health and Medical Research Council
Funding Amount
$385,115.00
Summary
Sight relies on the signals of nerve cells in the brain, but we know little about the way in which nerve cells support this, or why in some people sight is diminished. In this work we will measure the signals of nerve cells in the visual pathway to gain knowledge of these processes: we will make measurements in normal animals and in those that suffer from brain disorders. Our work will provide a scientific basis for the diagnosis and treatment of these disorders.
Normal hearing relies on the generation and transmission of electrical signals in the hearing organ, the inner ear. These electrical signals are generated by the action of specialized molecular ion channels in the cellular membranes of the inner ear and this research aims to charcterize these ion channels and detail their role in the hearing process. The results will impact on our understanding of human hearing disorders such as tinnitus, auditory neuropathy and disturbances of loudness sensatio ....Normal hearing relies on the generation and transmission of electrical signals in the hearing organ, the inner ear. These electrical signals are generated by the action of specialized molecular ion channels in the cellular membranes of the inner ear and this research aims to charcterize these ion channels and detail their role in the hearing process. The results will impact on our understanding of human hearing disorders such as tinnitus, auditory neuropathy and disturbances of loudness sensation.Read moreRead less
Novel Molecules Underlying The Development Of Corticopetal And Corticofugal Pathways
Funder
National Health and Medical Research Council
Funding Amount
$289,250.00
Summary
The mammalian brain consists of many discrete areas which perform specific functions. Each area has specific sets of connections with other brain areas. These sets of connections underlie the ability of the brain to execute functions critical to our daily lives, such as sight, hearing, touch and movement, as well as more complex functions such as memory, motivation and reasoning. We currently know little about how the sets of connections which underlie these functions are formed. The aim of this ....The mammalian brain consists of many discrete areas which perform specific functions. Each area has specific sets of connections with other brain areas. These sets of connections underlie the ability of the brain to execute functions critical to our daily lives, such as sight, hearing, touch and movement, as well as more complex functions such as memory, motivation and reasoning. We currently know little about how the sets of connections which underlie these functions are formed. The aim of this project is to understand how some of the connections between the cortex and other brain areas are formed during development. To do this the project will combine modern molecular techniques with neuroanatomy to identify molecules that are expressed by specific populations of neurons during critical developmental stages. These molecules will then be misexpressed in order to determine whether they are important for the development of appropriate connectivity in the brain. A knowledge of the molecules that regulate the development of neuronal pathways is critical to understanding brain development. In the long term, it will also lead to the development of therapies for cases when the brain is damaged or does not develop appropriately due to disease or injury.Read moreRead less