Innate Threat Detection Circuits In The Superior Colliculus Co-ordinate Respiratory And Cardiovascular Responses To Visual Stimuli
Funder
National Health and Medical Research Council
Funding Amount
$517,958.00
Summary
Our surroundings affect our bodies: light pollution, traffic, and aircraft noise all significantly affect cardiovascular health. This project will investigate interactions between brain systems that subconsciously scan our surroundings for interesting or threatening features, and those that co-ordinate the cardiovascular and respiratory systems. We will generate new knowledge that describes how the brain detects danger and translates this into signals that contribute to cardiovascular risk.
How The Lateral Habenula Integrates Behavioral And Autonomic Functions: The VTA Dopamine Connection
Funder
National Health and Medical Research Council
Funding Amount
$819,904.00
Summary
When adverse events occur, the lateral habenula, an old brain nucleus, helps calculate the wisest corrective action by contributing to the “brake” that controls the brain’s dopamine reward system. Our research will show how the lateral habenula links corrective changes in behavior with coordinated changes in temperature. Understanding this link will greatly contribute to understanding the brain mechanisms that regulate our physiology during stressful situations and as part of mental illness.
Determination Of Sympathetic Preganglionic Neuronal Phenotype
Funder
National Health and Medical Research Council
Funding Amount
$241,527.00
Summary
The nervous system is the single most complex part of our body. Its function depends on millions of connections between neurons, all of which must form correctly during development. Furthermore, each neuron must select a neurotransmitter with which to talk to its target neuron. A neurotransmitter is a chemical released from a neuron, which passes a signal to a target cell. Some neurotransmitters cause excitation of the target cell, others inhibition. Each neurotransmitter signals to the target c ....The nervous system is the single most complex part of our body. Its function depends on millions of connections between neurons, all of which must form correctly during development. Furthermore, each neuron must select a neurotransmitter with which to talk to its target neuron. A neurotransmitter is a chemical released from a neuron, which passes a signal to a target cell. Some neurotransmitters cause excitation of the target cell, others inhibition. Each neurotransmitter signals to the target cell via receptor molecule, matched to the neurotransmitter. Thus, a neuron is faced not only with making choices about what connections to make within the developing brain, but also it must select from a range of potential neurotransmitters and receptor molecules. We are interested in how neurons select the appropriate neurotransmitter. There are a number of ways that a neuron might be guided to the correct choice. It is possible that it could receive from the target cell a signal that guides the choice of neurotransmitter. We wish to examine this hypothesis to see if it is applicable to the autonomic nervous system, that part of the nervous system that controls functions like changes in blood pressure and heart rate. Our laboratory is expert in identifying the chemistry of autonomic neurons. We will use this knowledge to see what happens when we deliberately perturb the normal connections of autonomic neurons. Do they persist in expressing the neurotransmitters they would have done prior to the perturbation? Alternatively, do they adapt to the change of target via a signal received from the new target cell and express the appropriate phenotype? The results of these experiments will give insights into how the brain develops. The results will be important for both our basic understanding of biology and as a basis for the development of techniques for reversing neuronal damage.Read moreRead less
Neurogenic Hypertension In The Spontaneously Hypertensive Mouse : Role Of The Hypothalamic-brainstem Sympathetic Axis
Funder
National Health and Medical Research Council
Funding Amount
$475,917.00
Summary
In human high blood pressure, particularly in the young, an overactive nervous system is thought to be a major underlying cause. Using a unique mouse model of high blood pressure which closely resembles this aspect of the human disease, we will examine which brain cells and neuro- chemicals are involved, particularly in a small area that is involved in regulating the hormonal and nervous system response to stress. From this we hope to be able to target these chemicals with specific therapy.
G-alpha Proteins And Their Effectors (AC, PLC, Rho And ERK) In Central Cardiovascular Regulation In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$636,716.00
Summary
High blood pressure is a major risk factor for cardiovascular diseases such as stroke that are huge emotional and economic societal burdens. The brain is essential to the control of blood pressure. Specific sites within the brain are crucial in setting the resting level of blood pressure and controlling blood pressure in response to stimuli such as lying or standing. The activity of these brain sites is altered in conditions such as high blood pressure. We will determine the role specific protei ....High blood pressure is a major risk factor for cardiovascular diseases such as stroke that are huge emotional and economic societal burdens. The brain is essential to the control of blood pressure. Specific sites within the brain are crucial in setting the resting level of blood pressure and controlling blood pressure in response to stimuli such as lying or standing. The activity of these brain sites is altered in conditions such as high blood pressure. We will determine the role specific proteins within cells, which are important in cell to cell communication in the brain, have in the control of blood pressure. Cells in the brain communicate using chemical messengers that act at receptors on the cells surface. Three forms of these receptors exist. We are interested in the most abundant form of receptor that has about 860 members. When activated these receptors use a complex cascade of proteins within the cell to dictate that cell's response. We know that some of these receptors in the brain are involved in the regulation of blood pressure and that some of them are altered in conditions such as hypertension. We could target each of the receptors but for many of them we do not know the chemical than activates them. Fortunately each of 860 receptors act primarily via just a few specialised proteins. Initially we will target these proteins to determine the impact these receptors have in altering the resting levels of blood pressure, their role in response to stimuli that affect blood pressure and the role they play in hypertension. Three approaches will be used: altering function of the proteins, identifying the types of proteins present and identifying the cells involved, in brains sites important in regulation of the heart and blood vessels. This novel approach to understanding how the brain controls blood pressure will undoubtedly identify targets for novel blood pressure lowering therapies and targets for genetically determined causes of hypertension.Read moreRead less
A novel sensory neural circuit has been identified innervating the airways and lungs. The anatomical organisation of this circuit has been described to some extent in previous studies, however there is a significant gap in knowledge with respect to its functional importance. This project will develop methods to address this knowledge gap and in doing so the project will firstly describe how this circuit controls breathing under normal conditions and secondly how this becomes dysregulated during
Vasomotor Ganglionic Transmission: The Preganglionic Peptide And The Second Gear
Funder
National Health and Medical Research Council
Funding Amount
$451,896.00
Summary
Blood pressure depends on nerve signals that travel from the central nervous system to blood vessels. In the middle of this pathway is a relay station - the sympathetic ganglion cell. Transmission through this relay station has recently been shown to have not only a fixed but also a variable component - the 'second gear'. The project tests if and how three likely candidate peptide molecules, one in the nerves, two in the bloodstream, control this 'second gear' and hence regulate blood pressure.