Properties And Electro-Physiology Of The Intrinsic Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$419,214.00
Summary
The gut contains a very large number of nerve cells which fall into several functionally distinct groups. We have identified virtually all these functional groups in the guinea-pig small intestine and have begun an analysis of the ways the different groups communicate with each other. We have developed methods to identify the functions of any nerve cell from which we record and have also developed novel methods for specifically stimulating individual functional classes of nerve cells that contac ....The gut contains a very large number of nerve cells which fall into several functionally distinct groups. We have identified virtually all these functional groups in the guinea-pig small intestine and have begun an analysis of the ways the different groups communicate with each other. We have developed methods to identify the functions of any nerve cell from which we record and have also developed novel methods for specifically stimulating individual functional classes of nerve cells that contact them. The aim of the proposed research is to exploit these methods to identify the chemicals used by specifc types of nerve cell in transmission of information to other nerve cells during the normal behaviour of the intestine. We will record the behaviour of individual nerve cells in the gut wall while stimulating specific nerve pathways that contact them. We will then use drugs that block the activity of the chemicals of interest (small proteins called tachykinins, and certain amine compounds) to try and block the transmission of information between the nerve cells involved. Identification of the nature of the chemicals used at specific connections between different functional groups of nerve cells in the gut will allow the design of drugs for treatment of gastrointestinal disorders that will have minimal side effects. Further because the chemicals that are used for communication in the gut are also found in the brain, the results will provide evidence about the functions of these chemicals elsewhere in the nervous system.Read moreRead less
Peripheral Mechanisms Involved In Autonomic Hyperreflexia
Funder
National Health and Medical Research Council
Funding Amount
$229,917.00
Summary
Bladder distension or minor unheeded injuries below the lesion in spinally injured people often lead to episodes of high blood pressure that may cause stroke or death. These events require emergency hospitalization and are expensive as well as dangerous. After spinal injury, the control of sympathetic nerves that supply arteries and regulate blood pressure is lost. However, the nerves below the injury remain in place and the spinal cord below the lesion contains connections that can activate the ....Bladder distension or minor unheeded injuries below the lesion in spinally injured people often lead to episodes of high blood pressure that may cause stroke or death. These events require emergency hospitalization and are expensive as well as dangerous. After spinal injury, the control of sympathetic nerves that supply arteries and regulate blood pressure is lost. However, the nerves below the injury remain in place and the spinal cord below the lesion contains connections that can activate them. Signals from the bladder or skin enter the remaining lower part of the spinal cord and activate the sympathetic supply generating a rise in blood pressure. This project will test the hypothesis that increased sensitivity of arteries to the chemicals released from the sympathetic nerves leads to excessive vessel constriction, contributing to the exaggerated increase in pressure. We will investigate arteries removed from rats with experimental spinal transection. We will test the contractions of the arteries (a) to sympathetic nerve stimulation and (b) to the chemicals noradrenaline, adenosine 5'-triphosphate (ATP) and neuropeptide Y that are normally released during nerve activity. We will determine whether release of noradrenaline and ATP from nerves is normal or augmented using electrochemical and electrophysiological techniques. We will compare the responses with those in normal arteries, those in arteries whose nerves have been silenced by removing all connections from the spinal cord and those in arteries that have lost all their nerve supply. This will enable us to identify whether the mechanisms for release of transmitter substances are modified and whether the arterial muscle is hypersensitive to these substances. The results will help in the design of safer treatment for these potentially lethal emergencies in spinal patients.Read moreRead less
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