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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
Convergent Regulation Of Sympathetic Neuronal Excitability By Peptide Hormones And Transmitters
Funder
National Health and Medical Research Council
Funding Amount
$498,465.00
Summary
This project will examine how hormones involved in regulating blood pressure interact with the nerves that control blood flow to the gut. We will combine electrical recordings of the activity of single nerve cells with an innovative new method of optically tracking the movements of single molecules, including hormons and neuronal messengers, that send signals to the nerve cells. Our results will reveal how blood pressure is normally maintained at healthy levels, even if we are ill.
Does Pregnancy Cause Morphological Changes In Central As Well As Peripheral Nerve Pathways That Control Blood Pressure?
Funder
National Health and Medical Research Council
Funding Amount
$382,538.00
Summary
Pregnancy changes blood pressure but the mechanism is unknown. We will use state-of-the-art anatomical methods to define how pregnancy alters nerves controlling blood pressure. We will identify changes in the information the nerve cells receive, in their shape and in the way they communicate with other blood pressure-controlling nerve cells. This information will help to develop new ways to prevent and treat pre-eclampsia, a major cause of death and disability for mothers and their newborns.
After The Cloning Of The HMSNL Gene: Molecular Pathogenesis Of The Disease
Funder
National Health and Medical Research Council
Funding Amount
$258,564.00
Summary
We have completed an NHMRC-funded study, where we identified the gene for a severe disorder of the peripheral nervous system. The disease, hereditary motor and sensory neuropathy - Lom (HMSNL), presents with gait disturbances, difficulty in using the hands, muscle weakness and wasting and sensory loss. The concomitant impairment of the insulating myelin sheath surrounding nerve fibres (facilitating nerve conduction) and of the nerve fibres themselves suggests that the molecular defect lies in th ....We have completed an NHMRC-funded study, where we identified the gene for a severe disorder of the peripheral nervous system. The disease, hereditary motor and sensory neuropathy - Lom (HMSNL), presents with gait disturbances, difficulty in using the hands, muscle weakness and wasting and sensory loss. The concomitant impairment of the insulating myelin sheath surrounding nerve fibres (facilitating nerve conduction) and of the nerve fibres themselves suggests that the molecular defect lies in the basic mechanisms of interaction between the two main types of cell in the peripheral nervous system: the myelin-producing Schwann cell and the neuron. The two cells form the most complex system of communication in the human body, where signaling from one is vital for the development, functioning and survival of the other. Very little is known about the molecular mechanisms of this communication. At the same time, knowledge of the normal mechanisms of interaction is the key to better understanding of the mechanisms of disease in the peripheral nervous system and of the causes and possible prevention of the impairment of function. The newly identified HMSNL gene is probably involved in the signaling necessary for the development and functioning of the Schwann cell and for the survival of the nerve fibres. To gain an insight into the nature of the signaling cascade, we propose to use several complementary experimental approaches. We will create a mouse model of the human disease, to study its very early stages and subsequent evolution. In parallel, we will use molecular techniques and a yeast model, to identify other steps in the signaling cascade. The NHMRC-funded study will be part of a larger project conducted in collaboration with leading laboratories in the UK and the Netherlands, where other aspects of the molecular basis of the disease and of the role of the new gene will be examined.Read moreRead less