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
Modulation Of Autonomic Nerve Growth By Guidance Factors
Funder
National Health and Medical Research Council
Funding Amount
$393,277.00
Summary
Our goal is to understand how adult nerves are affected by injury so that we can devise therapies to make them regrow better. We will focus on nerves that control the urogenital organs because these are often injured during surgical procedures (e.g. prostatectomy, hysterectomy), with devastating effects on patients' quality of life. In this project we will investigate how naturally-occurring growth-inhibitory molecules affect nerve regrowth after injury in the pelvic nervous system.
Do Postjunctional Alterations Explain The Effects Of Diabetes On Neurovascular Transmission?
Funder
National Health and Medical Research Council
Funding Amount
$390,886.00
Summary
Diabetes produces disordered skin blood flow that increases risk of skin ulcers and gangrene. The project investigates nervous control of skin blood vessels in diabetes. It is assumed that all affects of diabetes on nerve function are explained by loss of nerves. We hypothesize that some affects of diabetes are due to dysfunction of blood vessels and not to nerve loss. The objective is to identify drug targets to improve blood flow in skin and thereby reduce the risk of skin ulcers and gangrene.
Neurotransmission In Functionally Distinct Vasodilator Pathways
Funder
National Health and Medical Research Council
Funding Amount
$809,934.00
Summary
A surprising feature of our body is that there is not enough blood to fully supply all our organs at once. This is why we sometimes faint when we are hot or get cramps when we are exercising. Consequently, the blood vessels change their diameter so that blood can be directed to the organs with greatest demand at any particular time. For example, if the vessel decreases in diameter, less blood flows through it, but if it increases in diameter, more blood flows through it to reach the appropriate ....A surprising feature of our body is that there is not enough blood to fully supply all our organs at once. This is why we sometimes faint when we are hot or get cramps when we are exercising. Consequently, the blood vessels change their diameter so that blood can be directed to the organs with greatest demand at any particular time. For example, if the vessel decreases in diameter, less blood flows through it, but if it increases in diameter, more blood flows through it to reach the appropriate organ. An important function of the nervous system is to control the flow of blood to different organs by changing the diameters of the blood vessels. One set of nerves decreases the diameter of the arteries, and another set of nerves increases the diameter. The nerves do this by releasing special combinations of chemicals when they get a message from the brain to do so. In this project we are especially interested in the nerves which increase blood flow to organs in the head and the pelvis. We will use a wide range of modern methods to find out how these nerves work. In some experiments, we will use sophisticated electrical equipment to measure just how the nerve cells controlling the diameter of the vessels respond to the instructions sent by the brain. In other experiments, we will find out which chemicals the nerves use to make the blood vessels increase in diameter. We also will discover how the various chemicals get released by the nerves at the right times, so that messages from the brain get to the blood vessels as efficiently as possible. One of the special parts of our project is that we will be able to observe directly the connections between the nerve cells and the blood vessels we are studying. Our results will be important for designing new drugs that could help people whose nerves are not working properly, such as in some patients with diabetes or vascular disease.Read moreRead less
Plasticity And Regeneration Of Bladder Motor Nerve Circuits After Injury
Funder
National Health and Medical Research Council
Funding Amount
$333,313.00
Summary
Our goal is to determine ways of improving the recovery of bladder-controlling nerves after they are injured, which has devastating effects on bladder function. This can happen because of lumbosacral spinal nerve damage or pelvic surgery. We also expect to establish broad principles that may be tested in other neurological conditions that affect bladder function, such as neurodegenerative disorders (e.g. diabetes) and spinal cord injury.
Mechanosensitive Afferent Nerves And Gastrointestinal Motility
Funder
National Health and Medical Research Council
Funding Amount
$384,693.00
Summary
This project aims to identify the different types of sensory nerves from the gut which cause sensations such as fullness, nausea or pain. These sensory nerves also activate important reflexes that coordinate different regions of the gut to ensure that food is properly digested and propelled. Many studies have examined these sensory nerves and how they can be activated by stretching the gut wall, but very basic questions remain to be answered. We do not know how many different types of sensory ne ....This project aims to identify the different types of sensory nerves from the gut which cause sensations such as fullness, nausea or pain. These sensory nerves also activate important reflexes that coordinate different regions of the gut to ensure that food is properly digested and propelled. Many studies have examined these sensory nerves and how they can be activated by stretching the gut wall, but very basic questions remain to be answered. We do not know how many different types of sensory nerves there are and whether they all respond to stretch in the same way. We cannot identify their specialised endings in the wall of the gut. While these sensory nerves definitely respond to stretch, they are also known to respond to contractions of the gut wall. Despite this, we do not understand how the normal movements of the gut wall activate them, nor why some movements can lead to pain. Most of the experiments will be carried out on small pieces of tissue taken from humanely killed guinea pigs and studied, under highly controlled conditions, in organ baths. The remainder of the study will be on specimens of human gut tissue obtained at surgery. This project will use new techniques to record sensory nerves during both stretch and contraction of the gut wall to understand what activates them. In addition, their endings will be labelled with dye to reveal their different shapes. Using computerised imaging techniques we will identify whether they respond to particular patterns of movement in the gut wall. Lastly we will record from these sensory neurones in live specimens of human colon to see whether the same types of sensory nerves are present in humans as in the small animals. This study will provide the first comprehensive account of sensory nerves to the gut wall that respond to distension, including those that activate pain pathways. This is a pre-requisite for designing new drugs that will target these nerve cells with minimal side effects.Read moreRead less
What Central Mechanisms Increase Cardiac Sympathetic Nerve Activity In Heart Failure?
Funder
National Health and Medical Research Council
Funding Amount
$401,389.00
Summary
Heart failure is a disabling and deadly syndrome that has reached epidemic proportions in western populations. In heart failure, the activity of the sympathetic nerves to the heart is dramatically increased, leading to development of arrhythmias and sudden death. Using our unique model of heart failure, in which we directly record cardiac sympathetic nerve activity, we aim to determine the mechanisms in the brain that cause this large, detrimental increase in nerve activity.
Morphological Determinants Of Neurotransmission In Autonomic Ganglia.
Funder
National Health and Medical Research Council
Funding Amount
$450,111.00
Summary
The nervous system consists of billions of nerve cells that are connected together in special ways to process information about the outside world and our internal state and then generate the appropriate responses of our body to this information. To understand the complex working of the brain and its nerves, we have to understand how all these nerves are connected to each other. We are interested in the nerves that control the functions of the internal organs, such as arteries, glands and the gut ....The nervous system consists of billions of nerve cells that are connected together in special ways to process information about the outside world and our internal state and then generate the appropriate responses of our body to this information. To understand the complex working of the brain and its nerves, we have to understand how all these nerves are connected to each other. We are interested in the nerves that control the functions of the internal organs, such as arteries, glands and the gut. The brain controls these functions automatically, so we usually are not directly aware of their activity. The instructions to change the activity of the internal organs are sent from the brain down the spinal cord. The information is then sent from the spinal cord to the organs via a special set of nerves. However, instead of going directly to their targets, these nerves make connections with yet another set of nerves, which then go on to make the final connections with the appropriate target organs. We know a lot about these final nerve cells, including how big they are, how complicated they look, and what kinds of chemicals they use to send messages to the organs that they control. However, we still do not very much about how all these nerves are connected to each other. In this project we will use different types of modern microscopes that use either lasers or electron beams to look directly at the nerves and their connections. We then will use computerised models to construct a detailed map of the pathways taken by the nerves on their way to their target organs. By knowing how the nerves are connected to each other in these pathways, we will be able to understand how the instructions of the brain are modified depending on what other things are going on in the body at the same time. This information will be vital to help us appreciate how the nerves work when we get sick or injured.Read moreRead less