Role Of Brain Serotonin In Animal Models Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$175,550.00
Summary
There is increasing evidence that deficiencies in the release of a brain chemical called serotonin play an important role in the development of schizophrenia. Post-mortem studies have shown changes in the levels of 'receptors' (keyholes for messenger chemicals in the brain) for serotonin in schizophrenia. In addition, in the treatment of schizophrenia, the more recently introduced 'atypical' antipsychotic drugs are superior to the more traditional 'typical' antipsychotics in terms of efficacy an ....There is increasing evidence that deficiencies in the release of a brain chemical called serotonin play an important role in the development of schizophrenia. Post-mortem studies have shown changes in the levels of 'receptors' (keyholes for messenger chemicals in the brain) for serotonin in schizophrenia. In addition, in the treatment of schizophrenia, the more recently introduced 'atypical' antipsychotic drugs are superior to the more traditional 'typical' antipsychotics in terms of efficacy and side-effect profile. Typical antipsychotic drugs act mainly through blockade of receptors for a brain chemical called dopamine. Atypical drugs appear to have additional actions, in particular blocking the effect of serotonin in the brain. This evidence is mostly circumstancial, relying to a large extent on biochemical analysis of brain regions and 'receptors' on which antipsychotics MAY act. It is currently unclear exactly how and where in the brain changes in serotonin activity influence behavioural processes causing schizophrenia. It is also unclear how and where typical and atypical antipsychotic drugs interact with the role of serotonin in schizophrenia. In this project we intend to inactivate specific parts of the serotonin system of otherwise intact, freely moving rats. Using behavioural observation methods relevant for schizophrenia, we will analyze if and how these interventions influence the behaviour of these rats. The results can have important implications for our fundamental understanding of the involvement of serotonin in the brain in schizophrenia.Read moreRead less
Neurophysiological Basis For Sensorimotor Interventions In Rehabilitation After Stroke
Funder
National Health and Medical Research Council
Funding Amount
$332,036.00
Summary
Stroke is estimated to cost the Australian government almost $2 billion annually, and is the most common cause of death after heart disease and cancer and one of the largest single causes of long-term disability. Of people who survive a stroke, a large number have some degree of residual motor dysfunction on one side of the body. Motor rehabilitation programmes are generally considered to enhance the recovery of motor function and to reduce the degree of long-term disability. However the rationa ....Stroke is estimated to cost the Australian government almost $2 billion annually, and is the most common cause of death after heart disease and cancer and one of the largest single causes of long-term disability. Of people who survive a stroke, a large number have some degree of residual motor dysfunction on one side of the body. Motor rehabilitation programmes are generally considered to enhance the recovery of motor function and to reduce the degree of long-term disability. However the rationale for the design of effective rehabilitation programmes is largely empirical, and there is uncertainty regarding the efficacy and cost-effectiveness of currently used therapies. The empirical nature of stroke rehabilitation has resulted in a diversity of techniques, many of which were pioneered 30-40 years ago, and which are generally aimed at enhancing brain plasticity as a means to facilitate motor recovery. However, despite the belief that brain plasticity is a key to recovery, it is still not known how best to develop this potential for reorganisation into practical interventions that could be introduced in stroke rehabilitation. The aim of the present study is to investigate the physiological bases for the action of commonly used sensorimotor rehabilitation strategies and identify those strategies which are most effective in bringing about corticomotor reorganisation, in the belief that such reorganisation is fundamental to motor recovery. Specifically we will investigate the changes in the organisation of the cortical projection to muscles of the upper limb as a result of passive movement, resisted and non-resisted movement, increased functional motor use and visuomotor training programmes. It is anticipated that the study will lead to a better understanding of the physiological basis for therapeutic interventions after stroke and will allow a more rational approach to the design of effective rehabilitation programmes for stroke patients.Read moreRead less
Neural Mechanisms Underlying Human Grasp And Manipulation
Funder
National Health and Medical Research Council
Funding Amount
$396,100.00
Summary
We rely on hand function in a multitude of simple tasks that we tend to take for granted but that are essential in our everyday lives; some examples are turning on a tap, doing up shoelaces, or holding a cup. Many people in the community are disabled by impaired hand function resulting from lesions of the central nervous system or peripheral nerve lesions. The size of the problem is enormous; manual dexterity is affected in approximately 20,000 new stroke patients each year in Australia as well ....We rely on hand function in a multitude of simple tasks that we tend to take for granted but that are essential in our everyday lives; some examples are turning on a tap, doing up shoelaces, or holding a cup. Many people in the community are disabled by impaired hand function resulting from lesions of the central nervous system or peripheral nerve lesions. The size of the problem is enormous; manual dexterity is affected in approximately 20,000 new stroke patients each year in Australia as well as in other neurological diseases such as neuropathies, nerve injuries, cerebral palsy and many others. The broad aim of this study is to investigate the poorly understood neural mechanisms that underlie sensorimotor control of hand function. We will target a specific aspect of manual dexterity that is crucial for the execution of common everyday tasks, like pouring liquid from a bottle, in which the digits are subjected to torsional loads. In order to maintain stable grasps, the motor control system must rapidly and automatically adjust the grip forces employed to meet the demands imposed by the changing torsion. This is only possible because of sensory feedback from the hand, a large component of which arises from the cutaneous mechanoreceptive afferent fibres. In the first two years we will use a combined approach of neural recording from peripheral nerves in anaesthetised monkeys and psychophysics experiments in normal humans to answer the general question: how does the population of cutaneous afferents provide precise feedback about torsion on the digits? In the third year we will perform key experiments in humans, using microneurography to record from their peripheral nerves. This will establish any differences between human and monkey mechanoreceptors.Read moreRead less
Plasticity Of Sensorimotor Representations In Adult Primate Cortex
Funder
National Health and Medical Research Council
Funding Amount
$554,656.00
Summary
Cells in some regions of the brain, collectively known as the sensorimotor cortex, control our capacity to purposefully move the arms and hands. Damage to these regions in adults causes severe deficits. However, rehabilitative training can restore some control over the muscles. To understand how the brain circuits change to compensate for injury, and what effect rehabilitation may have on these changes, I will study cellular alterations in the movement control pathways in the cerebral cortex.