Identifying Mechanisms That Increase The Pool Of Brain Wiring Proteins
Funder
National Health and Medical Research Council
Funding Amount
$445,093.00
Summary
The computational power of the brain is driven by its interconnected nerve cells. Defects in these connections can lead to neurological disease. This proposal seeks to identify new mechanisms for generating specific connections between nerve cells and thus establishing the proper neural circuitry in a healthy brain.
STK9, A Second Rett Syndrome Gene: Genetic And Functional Studies
Funder
National Health and Medical Research Council
Funding Amount
$468,750.00
Summary
Rett syndrome (RTT) is a devastating progressive disorder affecting motor and intellectual development. It is characterised by normal development for the first 6-12 months of life, followed by developmental regression with the loss of learned purposeful hand function, loss of acquired speech and communicative abilities, sometimes leading to the incorrect diagnosis of autism. It may be the most common cause of progressive mental retardation in girls, with an estimated prevalence in Australia of 1 ....Rett syndrome (RTT) is a devastating progressive disorder affecting motor and intellectual development. It is characterised by normal development for the first 6-12 months of life, followed by developmental regression with the loss of learned purposeful hand function, loss of acquired speech and communicative abilities, sometimes leading to the incorrect diagnosis of autism. It may be the most common cause of progressive mental retardation in girls, with an estimated prevalence in Australia of 1 per 10,000 females under the age of twelve years. It is a genetic disorder and occurs almost exclusively in females. In 1999, a gene (called MECP2) was identified which appears to be the cause of RTT in most girls and women with RTT. However, for 5 - 10% of RTT subjects, no gene change is found in the MECP2 gene, raising the possibility that other genes may also be responsible for RTT. Our research group has identified one of these genes. Known as STK9, little is known about this gene's function. Of great interest is the fact that our studies suggest that STK9 could also be a caus of intellectual disability in other patients, and with autism. The focus of this research project is to explore how common gene changes in STK9 are in a large number of children with RTT, intellectual disability and seizures, and autism with intellectual disability and seizures. Using cutting edge research technology, we will go on to study how STK9 interacts with MECP2 and other genes, in order to better understand how these genes may be detrimentally affecting brain function in girls and women with Rett syndrome and other neurological disorders. These studies will give us a greater understanding of normal brain development and function.Read moreRead less
Role Of Load Detection And Compensation In Pathogenesis Of Obstructive Sleep Apnea.
Funder
National Health and Medical Research Council
Funding Amount
$340,867.00
Summary
This proposal will use novel techniques to explore how defective responses to the threat posed by a collapsing upper airway contribute to the Obstructive Sleep Apnea syndrome, a disease involving repetitive collapse of the upper airway in sleep. Responses to small increases in the resistance to inspiratory airflow will be examined by measuring the small electrcal responses in the brain to these loads, and the response of the muscles responsible for maintaining airway patency to the collapsing fo ....This proposal will use novel techniques to explore how defective responses to the threat posed by a collapsing upper airway contribute to the Obstructive Sleep Apnea syndrome, a disease involving repetitive collapse of the upper airway in sleep. Responses to small increases in the resistance to inspiratory airflow will be examined by measuring the small electrcal responses in the brain to these loads, and the response of the muscles responsible for maintaining airway patency to the collapsing forces induced by these loads, in both wakefulness and sleep. The brain's response to resistive loads will also be evaluated using the techique of functional magnetic resonance imaging, which demonstrates areas of the brain activated by a stimulus.Read moreRead less
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
Cortical Interactions Of Parallel Afferent Channels Underlying Visual Perception, Attention And Memory
Funder
National Health and Medical Research Council
Funding Amount
$410,250.00
Summary
The visual pathways from the eyes to the brain consist of distinct groups of cells which are specialised to signal different aspects of the visual scene such as colour, contrast and movement. As the information they carry is relayed through and processed in many different regions of the brain these parallel information channels were, until recently, believed to remain completely separate from each other. Furthermore, it had been proposed that as the information reaches the visual neocortex the i ....The visual pathways from the eyes to the brain consist of distinct groups of cells which are specialised to signal different aspects of the visual scene such as colour, contrast and movement. As the information they carry is relayed through and processed in many different regions of the brain these parallel information channels were, until recently, believed to remain completely separate from each other. Furthermore, it had been proposed that as the information reaches the visual neocortex the information is channeled through two main largely parallel information processing streams, a dorsal stream to the parietal cortex (a where system) and a ventral stream to the temporal cortex (a what system). However, our recent functional studies (and anatomical studies from other laboratories) have indicated that the different information channels do interact already at a relatively early level of the visual pathway, namely in the primary visual cortex. We have shown this in two ways: (1) there is convergence of different information channels on individual neurones in the primary visual cortex; (2) signals from the faster where pathway comes back to the primary visual cortex to gate the slower channels going into the ventral what pathway. We have seen this occur in an attention paradigm and in a memory task. We will explore these interactions further to test hypotheses about: (1) how the convergence of different information channels relate to the functional and anatomical architecture of the visual cortex; (2) investigate at length the most poorly understood, the so-called koniocellular pathway from the retina to the cortex. This pathway seems to contain a specialised component which carries information about blue objects; (3) identify the source of the spotlight of attention we have discovered and (4) how and from where early visual structures receive the gating inputs in certain memory tasks.Read moreRead less
Identification Of Novel Regulatory Factors In Midbrain Development To Improve Cell Therapies For The Treatment Of Parkinson’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
Cell transplantation is one of the most promising therapeutic strategies for the treatment of Parkinson’s disease. Cells are transplanted directly into the brain of the patient and can compensate for those lost to the disease. In this project we are identifying new genes that regulate the normal development of the transplanted cells in mice. We hope to use this knowledge to improve the reliability and effectiveness of the approach, bringing the therapy closer to the clinic.
Cortical Interactions Between Afferent Channels In Macaque Visual System
Funder
National Health and Medical Research Council
Funding Amount
$380,154.00
Summary
There are three distinct groups of cells that carry the visual information from the eyes to the brain, each pathway signaling a different aspect of the visual scene. This project will study in detail the lesser known of these three pathways (koniocellular neurones): what sort of information they carry into the brain, how it is combined with the other pathways to yield our composite picture and where in the brain such combination takes place.
Epilepsy And Stress: An Explanatory Electrophysiological Model
Funder
National Health and Medical Research Council
Funding Amount
$100,233.00
Summary
Epilepsy is one of the most common recurrent neurological disorders worldwide, affecting between 1 and 2% of the population. The cascade of events culminating in epilepsy, or the role of seizures in altering brain structures and circuits has been difficult to define. Previous work from our group has shown that stress markedly accelerates the process of epilepsy development. I am developing a model of brain functioning from observed brain cells to chart the changes associated with seizures, stres ....Epilepsy is one of the most common recurrent neurological disorders worldwide, affecting between 1 and 2% of the population. The cascade of events culminating in epilepsy, or the role of seizures in altering brain structures and circuits has been difficult to define. Previous work from our group has shown that stress markedly accelerates the process of epilepsy development. I am developing a model of brain functioning from observed brain cells to chart the changes associated with seizures, stress, and potential treatments.Read moreRead less