Role Of The Hypothalamus, Oxidative Stress And Angiotensin In Chronic Stress
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Stress can trigger life threatening cardiovascular events and its impact is much greater when blood pressure is raised. We seek to determine which chemical type of brain neuron and which region is responsible for amplifying the responses to repeated stress in an animal model that closely resembles the human form of the disease. We will focus specifically on the hypothalamus which controls the sympathetic nervous system.
Generation Of Complex Responses In Retinal Ganglion Cells
Funder
National Health and Medical Research Council
Funding Amount
$490,500.00
Summary
The retinal ganglion cells, whose axons form the optic nerve, comprise numerous distinct types, which respond to visual stimuli in either a simple or complex manner. The project will investigate how the complex responses of the direction-selective ganglion cells (DSGCs) and the local-edge-detector ganglion cells (LEDs) are generated. It appears that the retinal neurons providing inhibitory input to DSGCs and LEDs use different neurotransmitters, and the project will investigate how this shapes t ....The retinal ganglion cells, whose axons form the optic nerve, comprise numerous distinct types, which respond to visual stimuli in either a simple or complex manner. The project will investigate how the complex responses of the direction-selective ganglion cells (DSGCs) and the local-edge-detector ganglion cells (LEDs) are generated. It appears that the retinal neurons providing inhibitory input to DSGCs and LEDs use different neurotransmitters, and the project will investigate how this shapes the response properties of the ganglion cells. This will be done both by recording the visually evoked responses of the ganglion cells in an isolated preparation of the retina and by using two-photon laser-scanning microscopy to functionally image the neuronal interactions between the neurons that inhibit the DSGCs.Read moreRead less
Multidimensional Coding Of Visual Information In The Retina
Funder
National Health and Medical Research Council
Funding Amount
$359,431.00
Summary
Although both the retina and visual cortex are part of the central nervous system, the coding of visual information in the two laminar structures differs markedly in that all three dimensions of the cortical sheet are used to code multiple response axes but only one dimension of the retinal sheet. This project examines how visual response properties are mapped through the depth of the retina and this will provide a comparatively simple paradigm of complex information processing in the brain.
Forebrain Neuroadaptations To Chronic Morphine Treatment
Funder
National Health and Medical Research Council
Funding Amount
$435,956.00
Summary
Drug addiction is caused by long term changes in brain areas that normally produce the drives that sustain normal behaviours such as eating, drinking and sex. Addictive drugs effectively hijack these brain areas so that behaviours relating to drug taking become associated with feeling good. In some individuals, over time the pattern of drug taking becomes compulsive and no longer can be controlled. This transition is now known to be due to drugs causing physical changes to certain groups of nerv ....Drug addiction is caused by long term changes in brain areas that normally produce the drives that sustain normal behaviours such as eating, drinking and sex. Addictive drugs effectively hijack these brain areas so that behaviours relating to drug taking become associated with feeling good. In some individuals, over time the pattern of drug taking becomes compulsive and no longer can be controlled. This transition is now known to be due to drugs causing physical changes to certain groups of nerve cells in the brain. The affected nerve cells are responsible for causing new behaviours that appear once addiction is established. Addiction is not exclusive to humans. Animals will self-inject the same addictive drugs that humans use, and show many other kinds of addictive behaviours that parallel aspects of human addiction. Studying the effects of addictive drugs on rats and other animals has been very important in working out where and how drugs work. We now have a very good idea of which parts of the brain are affected by drugs, and it turns out that most addictive drugs act in the same places. We also now know for all of the major drugs, exactly which parts of nerve cells they affect. However, this turns out to be only the first step as the nerve cells that directly respond to drugs can affect other whole networks of nerve cells. This study is going to look at how morphine, a drug that is related to heroin, affects nerve cells in a part of the brain that helps cause addiction. It is going to work out which of the many pathways in this brain region are affected by morphine treatments that cause addiction in rats. It will then see what is happening to single nerve cells in the affected pathways. If we can understand more about these processes it may become possible to come up with new ways to treat addiction. We will also understand much more about the production of powerful emotional and behavioural drives so many of us find hard to control.Read moreRead less
Mechanism Of Interaction Of VWC Domains And Consequence For Protein Function
Funder
National Health and Medical Research Council
Funding Amount
$516,803.00
Summary
More than 1000 proteins contain a type of module known as the VWC domain. These domains are discreet sections of the protein that are very important for how the protein works. Proteins containing this domain are involved in normal functioning of the human body and in diseases of the nervous system and blood, among others. The main function of the VWC domain is to link proteins together in complexes. How this is achieved is not known and is what we aim to discover.
Neural Coding Of A Cue To Auditory Space, In Noisy Environments
Funder
National Health and Medical Research Council
Funding Amount
$180,160.00
Summary
GENERAL BACKGROUND : Our ability to determine where a sound is coming from (localization ability) is severely disrupted when the environment is noisy. This affects our abilities at many ordinary tasks, such as keeping up a conversation in a noisy background, and also in other critical tasks (eg., in following warning signals in a noisy factory environment). In people who have some hearing loss, even if only partial deafness, localization ability is disrupted even when there is no noise in the ba ....GENERAL BACKGROUND : Our ability to determine where a sound is coming from (localization ability) is severely disrupted when the environment is noisy. This affects our abilities at many ordinary tasks, such as keeping up a conversation in a noisy background, and also in other critical tasks (eg., in following warning signals in a noisy factory environment). In people who have some hearing loss, even if only partial deafness, localization ability is disrupted even when there is no noise in the background, and is even more severely disrupted when the environment is noisy. SCIENTIFIC BACKGROUND : Our localization ability depends on the way neurons in the brain code the position of a source of sound we wish to detect. From studies in animals we know a lot about the way in which neurons do this coding in silence. However, we know almost nothing about how this coding is affected by a noisy background. Further, we know absolutely nothing about how this coding, whether in silence or when there is noise, is affected when there is also a hearing loss. SIGNIFICANCE : If we are to understand the effects of hearing losses on coding of the location of a sound signal we need to know first how noise affects the coding in cases of normal hearing. This project aims to gain that information. I will then extend this to studying the detailed basis of these effects, ie., exactly what mechanisms are affected in the neurons. Then I will determine how noise from different positions affects the coding of signal sounds at differnt positions. These data will provide us the essential base from which we can, later, go on to study how noise affects coding by neurons of the location of a signal. I plan to increase the value of the current study by developing, from the data gained in the studies in animals, computer-based models that will allow us to predict how coding of sound signal location is affected by hearing loss, and how this is exacerbated by noisy environments.Read moreRead less
Development Of Executive Functions In Children With Frontal Lobe Lesions
Funder
National Health and Medical Research Council
Funding Amount
$160,379.00
Summary
Executive functions (EF), refer to the ability to problem solve, think flexibly and in abstract terms and pay attention. EFs are essential for managing daily life activities. The frontal lobes of the brain are believed be important in coordinating EFs. In childhood, frontal areas are developing rapidly and damage may affect ongoing development due to impairments in a child's capacity to function normally within their environment, interfering with adaptive functions such as new learning and reaso ....Executive functions (EF), refer to the ability to problem solve, think flexibly and in abstract terms and pay attention. EFs are essential for managing daily life activities. The frontal lobes of the brain are believed be important in coordinating EFs. In childhood, frontal areas are developing rapidly and damage may affect ongoing development due to impairments in a child's capacity to function normally within their environment, interfering with adaptive functions such as new learning and reasoning. Executive dysfunction in children manifests as disorganisation, impulsivity, inattention and inappropriate behaviour. Such problems are often masked in early chilhood, due to highly structured environments and support of parents and care-givers in day-to-day activities. However, as children mature, expectations of indepence increase and executive deficits become more apparent (ie. child 'grows into' these problems). Appropriate treatment and management is dependent on (i) improvement in early identification of patients at risk for such sequelae; (ii) establishing long-term consequences of executive deficits to ongoing development. This research aims to advance our understanding of EFs and their development through childhood, both in healthy children and children with cerebral lesions to regions believed to subsume EFs(ie the frontal lobes). While anecdotal case data is available, to our knowledge, no other study has attempted to do this using a longitudinal group design. Specific predictions include; (i) Children with frontal lobe damage will perform more poorly on EF measures, in comparison to children with damage to other cerebral areas and healthy children; (ii) Children with frontal lobe damage will show increasing deficits on EF tasks over time, reflecting an inability to acquire executive skills in the expected time frame, when compared with children with localised damage to cerebral areas excluding the frontal lobes, and healthy children.Read moreRead less
THE AUTONOMIC, SOMATIC AND CENTRAL NEURAL RESPONSES TO DEEP AND SUPERFICIAL PAIN IN HUMAN SUBJECTS
Funder
National Health and Medical Research Council
Funding Amount
$375,750.00
Summary
Pain is a subjective experience, the intensity of which can be readily influenced by personal experience. Despite this, pain originating from a particular part of the body will usually be described by all individuals as having similar character. For example, pain arising from the skin is commonly described as being sharp or burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and diffuse. In addition to producing sensory changes, pain also evokes ....Pain is a subjective experience, the intensity of which can be readily influenced by personal experience. Despite this, pain originating from a particular part of the body will usually be described by all individuals as having similar character. For example, pain arising from the skin is commonly described as being sharp or burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and diffuse. In addition to producing sensory changes, pain also evokes changes in blood pressure, heart rate and motor activity (often in an attempt to remove the source of the pain). The proposed research aims to characterise the cardiovascular and motor patterns associated with pain originating in skin and in muscle and to examine the brain regions that produce these changes. More specifically, microelectrodes will be used to investigate changes in peripheral nerve activity during transient painful skin and muscle events in awake human subjects. In a separate investigation functional magnetic resonance imaging will be used to determine brain sites that are activated by skin or muscle pain.Read moreRead less
Anatomical Substrates For Primate Executive Cortical Function
Funder
National Health and Medical Research Council
Funding Amount
$362,820.00
Summary
When studying the brain, many have been tempted to look for similarities in organization of cells and circuitry in different regions involved in various processes. While, at a first approximation, this may be a reasonable approach to understand how the brain works, it also ignores what makes the brain so complex: the diversity in its structure. In the late 19th, and early 20th, centuries, pioneering anatomists seized on the diversity in structure of the human brain. The study of cortical circuit ....When studying the brain, many have been tempted to look for similarities in organization of cells and circuitry in different regions involved in various processes. While, at a first approximation, this may be a reasonable approach to understand how the brain works, it also ignores what makes the brain so complex: the diversity in its structure. In the late 19th, and early 20th, centuries, pioneering anatomists seized on the diversity in structure of the human brain. The study of cortical circuitry that underlies the diversity in cortical processing reached a zenith and there was a renaissance in understanding of brain function. These researchers were, however, limited by techniques available to them at the time. With the advent of new methodologies which allowed scientists to explore individual connections between cells (synapses), to probe structure and transmission across synapses, and to record from live neurones, new and exciting discoveries were made. However, these methodologies are highly time consuming and studies became necessarily more focussed. As a result, there was a tendency in the later half of the 20th century to extrapolate findings from one cortical area to cortex in general. Even more precarious, anatomical and functional findings in highly specialized sensory cortex of one species were projected to other distantly related species. Such thinking lead to a dark age in neuroscience. It became widely accepted that there exists a canonical circuit. Consequently, differences in function between different cortical areas were attributed solely to the source of their projections. The central thesis of this project is to study aspects of cell structure and cortical circuitry in the prefrontal lobe. We hope that the project will provide another step in the pathway that leads to understanding the mind.Read moreRead less
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