Differentiation Of Respiratory Behaviour In The Mammalian Fetus
Funder
National Health and Medical Research Council
Funding Amount
$434,839.00
Summary
Mammalian fetuses are highly active from early in gestation, manifesting patterns of activity that are gradually transformed throughout fetal life, ultimately producing a repertoire of behaviours essential for postnatal survival. These behaviours are of fundamental importance to animals, and none more so than breathing which must perform effectively from the moment of birth. We plan to examine neural control mechanisms that transform a primitive pattern of breathing in the early gestation fetus ....Mammalian fetuses are highly active from early in gestation, manifesting patterns of activity that are gradually transformed throughout fetal life, ultimately producing a repertoire of behaviours essential for postnatal survival. These behaviours are of fundamental importance to animals, and none more so than breathing which must perform effectively from the moment of birth. We plan to examine neural control mechanisms that transform a primitive pattern of breathing in the early gestation fetus into the functional form that effectively ventilates the lungs after birth. In addition to examining the prenatal development of breathing, our program will focus on the developmental fate of a transient behaviour restricted to early development. This early behaviour plays a fundamental role in the development of the motor system before being extinguished under the influence of supraspinal inputs. This program will therefore provide a basis for understanding the mechanisms by which the brain establishes control of the motor circuits of the spinal cord during development. Further, the program is designed to provide a basis for understanding the respiratory problems so common in the preterm human infant.Read moreRead less
Cortical Plasticity And Fine Motor Skills In Older Adults
Funder
National Health and Medical Research Council
Funding Amount
$244,255.00
Summary
Even in healthy individuals, the ageing process is usually associated with a progressive reduction in the performance of various motor skills, such as writing, placing keys in keyholes and fastening buttons. These deficits in manual performance may be due to an age-related decline in the ability of the brain to modify its connections (plasticity) when learning new motor skills. This brain plasticity is a fundamental property of the nervous system, where it is critical for learning and memory, bu ....Even in healthy individuals, the ageing process is usually associated with a progressive reduction in the performance of various motor skills, such as writing, placing keys in keyholes and fastening buttons. These deficits in manual performance may be due to an age-related decline in the ability of the brain to modify its connections (plasticity) when learning new motor skills. This brain plasticity is a fundamental property of the nervous system, where it is critical for learning and memory, but is also important for recovery from brain injury. The goal of the proposed studies is to examine the extent of brain plasticity when performing fine motor skills in older adults, and relate this to motor performance and learning in the elderly. We will use three complementary approaches that will employ novel techniques of magnetic brain stimulation to achieve this goal. These studies will be the first to ascertain a link between deficits in brain plasticity and impaired manual performance in older adults. Furthermore, these studies will be the first to examine interventions designed to promote brain plasticity and motor performance in older adults. Because the majority of patients requiring neurological rehabilitation are in an older age group, it is important to understand the extent of brain plasticity in the elderly. This new information may ultimately lead to innovative therapeutic or rehabilitation strategies to retain or improve fine motor skills in the elderly and promote functional recovery from brain injury.Read moreRead less
Motor Unit Synchronisation And Neuromuscular Performance
Funder
National Health and Medical Research Council
Funding Amount
$198,500.00
Summary
The fine control of force is important for many everyday tasks such as writing, grasping objects between index finger and thumb, and fastening buttons. Factors that influence the ability to control force include the coordinated activation of groups of muscle fibres called single motor units. This proposal focuses on the concept that the coordinated activation of motor units is influenced by muscle activity and can impair the ability to produce finely controlled muscle contractions. The goal of t ....The fine control of force is important for many everyday tasks such as writing, grasping objects between index finger and thumb, and fastening buttons. Factors that influence the ability to control force include the coordinated activation of groups of muscle fibres called single motor units. This proposal focuses on the concept that the coordinated activation of motor units is influenced by muscle activity and can impair the ability to produce finely controlled muscle contractions. The goal of these studies is to explore the boudary conditions of the adaptive nature of the nervous system to examine how coordinated motor unit activity influences these aspects of neuromuscular performance. The outcomes of these experiments will identify if altering muscle activity influences the control of movement by altering single motor unit activity. These results will have direct application to the interpretation of abnormal movement control and tremor that is observed in certain neurological diseases such as Parkinson's disease. Furthermore, new information will be gained on the adaptability of the motor system and its role in the execution of fine motor tasks that may aid in the development of rehabilitation strategies following stroke or spinal cord injury.Read moreRead less
Is EphA4 The Major Molecular Regulator Of Axonal Regeneration?
Funder
National Health and Medical Research Council
Funding Amount
$491,000.00
Summary
Spinal cord injury affects a substantial number of Australians each year. Around half the number of spinal cord injury cases result in quadriplegia, with loss of function to a varying degree in the upper as well as the lower limbs. The limited degree of repair of spinal axons following injury means that such paralysis is usually permanent. Although the inability to walk is a serious issue, the limited function of the arms and hands results in a loss of independence which is a major factor contri ....Spinal cord injury affects a substantial number of Australians each year. Around half the number of spinal cord injury cases result in quadriplegia, with loss of function to a varying degree in the upper as well as the lower limbs. The limited degree of repair of spinal axons following injury means that such paralysis is usually permanent. Although the inability to walk is a serious issue, the limited function of the arms and hands results in a loss of independence which is a major factor contribuing to the enormous personal, financial, and community costs of this problem, estimated to cost the Australian community $200 million a year. In recent years advanced anatomical and molecular approaches to the problem of repair of the central nervous system have provided great insights into the neuronal and glial reactions to neural damage that appear to govern the success or failure of neural regeneration. Our preliminary data indicate that a receptor tyrosine kinase, EphA4, which is important for axonal pathfinding in the developing nervous system, is a potent inhibitor of neural regeneration following spinal cord injury. In this project we will determine the mechanisms by which EphA4 exerts its inhibitory effects, and examine the effect of neutralizing EphA4 signalling on neural regeneration. Success in achieving this result will lead to the development of a therapeutic intervention that we will test in mouse models.Read moreRead less
The Pathogenesis Of Motor Neuron Degeneration Caused By A Triplet Repeat Expansion In The Androgen Receptor Gene.
Funder
National Health and Medical Research Council
Funding Amount
$284,748.00
Summary
Male sex hormones, or androgens, work by binding to a specific receptor, known as the androgen receptor. Androgens have an important and yet poorly understood role in nerve function. Our research is investigating how a genetic mutation in the androgen receptor causes Kennedy?s disease. This is a rare disease, affecting adult males, which causes nerves to die. The nerves which are affected are those supplying our muscles, called motor neurons. This leads to muscle wasting in the face and body. Ot ....Male sex hormones, or androgens, work by binding to a specific receptor, known as the androgen receptor. Androgens have an important and yet poorly understood role in nerve function. Our research is investigating how a genetic mutation in the androgen receptor causes Kennedy?s disease. This is a rare disease, affecting adult males, which causes nerves to die. The nerves which are affected are those supplying our muscles, called motor neurons. This leads to muscle wasting in the face and body. Other symptoms include testicular wasting, reduced fertility and breast tissue enlargement. It is currently not known what causes motor nerves to degenerate in Kennedy?s disease. We are endeavouring to investigate the cause of Kennedy?s disease via the generation of a transgenic mouse carrying this mutation. It is only through a studying transgenic mouse affected by this disease can we begin to understand what is happening to nerves to cause them to die, and importantly, how can we prevent them from dying. These studies will also provide crucial information on the effects of sex hormones on nerves. As there is currently no treatment for Kennedy?s disease, an aim of this project is to investigate how we can treat this disease. This will be the first time that we can systemically test potential treatments and work toward preventing the degeneration of these nerves. Kennedy?s disease is related to a number of other neurodegenerative diseases including Huntington?s disease, which are caused by similar genetic mutations. All of these diseases are caused by degeneration of specific nerve cells. Evidence suggests that there may be similar mechanisms involved in all of these diseases. The results of this study will therefore help us to understand a range of diseases and may eventually lead to the development of therapeutic strategies to prevent their debilitating effects.Read moreRead less
The Use Of Soluble Antagonists Of EphA4 In Spinal Cord Injuries
Funder
National Health and Medical Research Council
Funding Amount
$622,361.00
Summary
Permanent and limited recovery of function following spinal cord injury is a direct result of the lack of nerve regrowth through the injury. Our preliminary data suggest that antagonising the effects of EphA4, a protein involved in brain development, leads to substantial functional recovery simultaneous with nerve regrowth. In addition to designing new, more effective blockers of EphA4, we will study the signalling pathways that EphA4 activates to inhibit nerve regrowth.
Pain changes movement. Although undisputed, there is a surprising lack of agreement regarding the underlying mechanisms. This project involves an innovative mix of neurophysiological methods to investigate the drive to muscle cells from the nervous system and changes in the mechanics of contraction. These studies will resolve the perplexing problem of how pain changes our ability to activate muscle. Clear understanding of the underlying mechanisms can guide rehabilitation.