Neurodevelopmental Role Of Susceptibility Genes For Autism Spectrum Disorders: From Genes To Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$482,968.00
Summary
Autism is a developmental neuropsychiatric syndrome characterised by impairments in three principal domains: social interaction, language and behavioural inflexibility. Autism spectrum disorder (ASD) refers to a group of neurodevelopmental syndromes with the common feature of dysfunctional reciprocal social interaction. In this project we will investigate the role of genes that increase the risk of ASD in the development of behaviours using an animal model. This work will lead to a better unders ....Autism is a developmental neuropsychiatric syndrome characterised by impairments in three principal domains: social interaction, language and behavioural inflexibility. Autism spectrum disorder (ASD) refers to a group of neurodevelopmental syndromes with the common feature of dysfunctional reciprocal social interaction. In this project we will investigate the role of genes that increase the risk of ASD in the development of behaviours using an animal model. This work will lead to a better understanding of the genetic basis of ASD.Read moreRead less
Promoting Plasticity And Functional Recovery In The Adult Brain: Enrichment And Transcranial Magnetic Stimulation
Funder
National Health and Medical Research Council
Funding Amount
$402,493.00
Summary
The adult human brain is unable to repair itself: axons do not regenerate effectively and there is limited reorganisation of remaining projections. Our research directly addresses how to form anatomically accurate and thus functionally useful networks through improving axonal regeneration per se, but more importantly it investigates clinically relevant, non-invasive methods that encourage the remaining nerve cells to reorganise, maximising the surviving resources of the damaged brain.
A Brain-Based Measure Of Anxiety Sensitivity: Validation Of A Novel Intermediate Phenotype With Psychophysiologically-Informed Neuroimaging
Funder
National Health and Medical Research Council
Funding Amount
$271,930.00
Summary
Excessive anxiety is disabling, such that people who suffer from a clinical anxiety disorder are often crippled by overwhelming emotional and physical symptoms. We will use sophisticated brain imaging technology to understand how certain brain areas produce feelings of anxiety, including a common fear of arousal related bodily sensations. This work is expected to enhance our basic understanding of the brain basis of anxiety symptoms and may inform new treatment options with biological rationale.
Regulation Of Pre-mRNA And MRNA Processing By The Neuron-specific Hu RNA-binding Proteins
Funder
National Health and Medical Research Council
Funding Amount
$477,750.00
Summary
The precise control of protein expression is absolutely critical in biology, and the key decisions about which genes are turned on or off at any one moment control the proper growth and maturation of an organism during development, and are responsible for the organism's homeostasis and proper response to environmental changes as an adult. Many gene expression programs are highly complex and controlled by regulating the activation of individual genes as they are copied from DNA to RNA. However, t ....The precise control of protein expression is absolutely critical in biology, and the key decisions about which genes are turned on or off at any one moment control the proper growth and maturation of an organism during development, and are responsible for the organism's homeostasis and proper response to environmental changes as an adult. Many gene expression programs are highly complex and controlled by regulating the activation of individual genes as they are copied from DNA to RNA. However, this activation is just the start of the process to produce an active protein. In higher organisms, these RNA copies almost always contain interruptions called introns, which must be excised from the RNA. Also, protein factors bound to specific RNAs can dictate whether the RNA is used to make protein or not, and these factors can also affect the localisation of the RNA to a specific sub-cellular destination, giving rise to highly localised protein expression. Evidence suggests that neurons are a cell type that rely heavily on mechanisms of RNA regulation. During development neurons become highly polarised, acquiring an axon which can elongate and find distant synaptic targets. While much is known about how axon growth cones respond to various guidance cues, the mechanisms by which the axon is able to translate this guidance cue information into structural changes which allow the growth cone to expand or collapse is largely unexplored. Recent evidence suggests that accurate growth cone guidance is absolutely dependent upon local protein synthesis. The functional corollary of this finding is that axon guidance requires RNA localisation and control of protein synthesis of RNAs in the growth cone. This phenomenon of spatial gene regulation within an individual cell is a central research interest for understanding how the brain functions.Read moreRead less
Using Contextual Effects To Test Theories Of Coding In Visual Cortex
Funder
National Health and Medical Research Council
Funding Amount
$200,500.00
Summary
The visual cortex is the main structure in the brain that processes the visual scene. Cells in the cortex respond selectively to features of the scene such as the orientation of objects, the direction they move and their brightness relative to the background. Cortical cells are arranged in a topographic map of visual space, so that nearby cells respond to light from nearby parts of the image. Recent advances have shown that cells talk to each other so a stimulus in one part of the visual field c ....The visual cortex is the main structure in the brain that processes the visual scene. Cells in the cortex respond selectively to features of the scene such as the orientation of objects, the direction they move and their brightness relative to the background. Cortical cells are arranged in a topographic map of visual space, so that nearby cells respond to light from nearby parts of the image. Recent advances have shown that cells talk to each other so a stimulus in one part of the visual field can influence the responses of cells looking at other regions. This communication between cells is important in guiding the brain to focus on areas of the visual scene that are most important, a process known as attention. An example would be that a mouse moving through the periphery of someone's vision would attract their attention away from objects elsewhere in the scene. This project is designed to study the way that cells in the visual cortex cooperate to guide attention. Attention is important because it reduces the need to process all the detail in the visual scene with the same level of accuracy, leaving more resources free to process what is important. Attention deficits are a problem for people with dyslexia, so understanding the physiological basis of attention is an important goal. As well as attention, the visual system has a range of other mechanisms to select important information from the visual scene. For example, visual adaptation tends to improve the ability to code changes in the visual scene at the expense of reducing the sensitivity of the system overall. This project will investigate the relationship between attentional and adaptive mechanisms in the visual cortex. We expect to establish the precise physiological mechanisms that drive adaptive and attentional mechanisms in the mammalian brain.Read moreRead less
Brain Angiotensin: Generation, Localisation And Physiological Function
Funder
National Health and Medical Research Council
Funding Amount
$209,250.00
Summary
The renin angiotensin system is one of the major homonal systems of the body that regulate the cardiovascular system and bodily salt and water balance. Drugs that inhibit the function of this system by reducing the blood level of the hormone angiotensin II or blocking the receptors at which it acts are in the forefront of treatment of high blood pressure and heart failure. It has been proposed that a separate brain renin angiotensin system exists that is not influenced by angiotensin II in the b ....The renin angiotensin system is one of the major homonal systems of the body that regulate the cardiovascular system and bodily salt and water balance. Drugs that inhibit the function of this system by reducing the blood level of the hormone angiotensin II or blocking the receptors at which it acts are in the forefront of treatment of high blood pressure and heart failure. It has been proposed that a separate brain renin angiotensin system exists that is not influenced by angiotensin II in the blood stream because of the blood-brain barrier. Strains of mice in which the genes that code for two components of this system - angiotensin converting enzyme (the enzyme responsible for generating angiotensin II) and angiotensinogen (the protein which gives rise to angiotensin II) provide excellent tools to elucidate this system in the brain. By studying these mice we will be able to determine whether angiotensin converting enzyme is necessary in the brain for foreming angiotensin II, and we will be able to determine the sites in the brain where authentic angiotensin peptides exist. We will also determine whether angiotensin II transmits information between neurons in the brain that play a role in control of the cardiovascular system and body fluid balance.Read moreRead less
Quantifying The Neurocognitive Impact Of Cannabis Across The Life Span: The Evolution Of Memory Deficits.
Funder
National Health and Medical Research Council
Funding Amount
$516,572.00
Summary
Cannabis is the most widely used illicit substance, and its use is particularly prevalent during adolescence and young adulthood. Adolescence is also a period when the brain undergoes significant structural and functional change, and there is growing evidence that the brain may be particularly vulnerable to the effects of addictive substances during this developmental stage. There is increasing evidence that long term or heavy use of cannabis impairs learning and memory. It is thought that the c ....Cannabis is the most widely used illicit substance, and its use is particularly prevalent during adolescence and young adulthood. Adolescence is also a period when the brain undergoes significant structural and functional change, and there is growing evidence that the brain may be particularly vulnerable to the effects of addictive substances during this developmental stage. There is increasing evidence that long term or heavy use of cannabis impairs learning and memory. It is thought that the continued bombardment of the brain s own natural cannabis-like neurotransmitter system by the active chemicals within cannabis disrupts critical aspects of brain function. This research seeks to improve our understanding of the way that cannabis use affects memory and how these problems might develop or worsen from adolescence to adulthood. This project will investigate memory processes in cannabis users using functional brain imaging techniques. This will allow identification of regions of the brain that are not working efficiently when cannabis users attempt to memorise and recall words from a list and recognise patterns. The project will examine how different levels of cannabis use (long term vs. short term and heavy vs. light) may affect brain function during learning and memory, and determine if the observed memory problems depend upon the age at which cannabis use began and the gender of the user. The findings from this research will substantially contribute to our understanding of the ways in which cannabis use affects brain function and potentially triggers serious psychiatric disorders, such as schizophrenia. The findings will contribute to guidelines regarding hazardous levels of cannabis use within adolescent and adult populations, and will inform debate, policy, education and treatment.Read moreRead less
An Integrated Psychoacoustic And High-field FMRI Study Of Auditory Temporal Processsing Dysfunction In Schiophrenia.
Funder
National Health and Medical Research Council
Funding Amount
$306,000.00
Summary
This research seeks to improve our understanding of the causes of brain dysfunction in schizophrenia. This chronic and debilitating psychiatric disorder is usually accompanied by dramatic symptoms such as hallucinations, delusions, paranoia and disordered patterns of thinking. Based on our interpretation of evidence from a number of fields of schizophrenia research we suspect that the brain dysfunction in schizophrenia may not in the brain areas responsible for those dramatic symptoms but occurs ....This research seeks to improve our understanding of the causes of brain dysfunction in schizophrenia. This chronic and debilitating psychiatric disorder is usually accompanied by dramatic symptoms such as hallucinations, delusions, paranoia and disordered patterns of thinking. Based on our interpretation of evidence from a number of fields of schizophrenia research we suspect that the brain dysfunction in schizophrenia may not in the brain areas responsible for those dramatic symptoms but occurs initially in the very basic sensory regions of the brain. These regions can be thought of as providing the building blocks of our perceptions, that ultimately allow us to see, hear, smell and feel. Our previous research shows that people with schizophrenia have a very specific problem in the way that they perceive sounds. Using measures of brain activity, people with schizophrenia show consistent evidence that their brains do not process some of the timing information contained in sound. This is not the same as saying that people with schizophrenia are deaf, the deficits we see are much more subtle. It's a bit like the chaos theory analogy of a butterfly fluttering in Brazil and causing a typhoon in China. We think that very small alterations in brain activity in the initial stages of sensory processing can cascade through successively more complex stages of the brain, eventually creating the psychotic storm that becomes evident as the primary symptoms of schizophrenia. The brain regions we are interested in are located down at the base of the brain, in the brainstem, and it is only recently that the technology and methods of analysis we need to look at this activity have been developed. In this research we will be using functional magnetic resonance imaging and sophisticated hearing tests to examine whether these brain regions show the alterations we expect. If so, this will mean that the brain dysfunction in schizophrenia is quite different to what is currently believed.Read moreRead less
Mechanisms Contributing To Long-term Neuronal Loss After Hypoxia-ischemia In The Premature Neonate Brain.
Funder
National Health and Medical Research Council
Funding Amount
$432,535.00
Summary
A lack of oxygen (hypoxia) and blood flow to the brain (ischemia) around the time of birth can cause brain injury that perists into adulthood. The burdens on financial, educational and healthcare resources are enormous. We will improve our understanding of what parts of the brain are injured and the mechanisms contributing to on-going brain injury after hypoxia-ischemia.This is important to devise treatments and to provide a healthy start to life for neonates.
Orientation-specific Contextual Modulation In Human Visual Cortex
Funder
National Health and Medical Research Council
Funding Amount
$290,413.00
Summary
Context has a strong infuence on our visual perception. We will study patterns of activity in the normal human brain to identify the cortical signature of contextual modulation in vision. The correspondences between patterns of brain activity and visual perception in the normal human brain will provide data against which brain activity in disorders such as schizophrenia and bipolar disorder can be assessed.