Membrane excitability and cellular calcium regulation in the peripheral nervous system under different (patho)-physiological conditions and in inflammatory disease. Studies of cytokine action on neurons and muscle give new insights into functional responses of the nervous system to systemic inflammation and sepsis. In some countries, sepsis is the third most frequent cause of death following heart attack. Elucidating the pathomechanisms allows to develop therapeutic strategies. Electrophysiology ....Membrane excitability and cellular calcium regulation in the peripheral nervous system under different (patho)-physiological conditions and in inflammatory disease. Studies of cytokine action on neurons and muscle give new insights into functional responses of the nervous system to systemic inflammation and sepsis. In some countries, sepsis is the third most frequent cause of death following heart attack. Elucidating the pathomechanisms allows to develop therapeutic strategies. Electrophysiology, Ca2+ regulation and optical membrane potentiometry allow us to monitor early changes in disease on a (sub)cellular level. Experiments on Ca2+ regulation and ion channel function in muscle with different cholesterol membrane contents will help to understand pathomechanisms in high cholesterol diseases, e.g. obesity, on the membrane level long before cardiovascular effects become prominent.Read moreRead less
Understanding how the brain uses sensory information to guide reaching and grasping movements. Reaching, grasping and manipulating objects are crucial aspects of our daily lives, which are performed so effortlessly that they tend to be taken for granted. We know however that these functions take a relatively long time to mature (think of a baby learning how to get an object), and that they can be impaired by brain lesions involving a region called the posterior parietal cortex. We also know that ....Understanding how the brain uses sensory information to guide reaching and grasping movements. Reaching, grasping and manipulating objects are crucial aspects of our daily lives, which are performed so effortlessly that they tend to be taken for granted. We know however that these functions take a relatively long time to mature (think of a baby learning how to get an object), and that they can be impaired by brain lesions involving a region called the posterior parietal cortex. We also know that this region has multiple subdivisions, but how exactly these interact in allowing the sensory information to guide arm and hand muscles is unknown. Discovering how this happens in terms of cellular interaction can have profound implications for the creation of new technologies such as artificial limbs and autonomous robots, and result in health benefits.Read moreRead less
Relationship of the functional architecture of the mammalian brain to its microcircuitry. The project seeks to understand a very fundamental issue in neuroscience: how the connectivity and architecture of the cortex are related to the functions of neurones in that area? This will be investigated by imaging the surface of the visual cortex of anaesthetised cats and monkeys as special visual patterns are shown to the eye/s. The overall picture gained of the active and inactive cortical areas will ....Relationship of the functional architecture of the mammalian brain to its microcircuitry. The project seeks to understand a very fundamental issue in neuroscience: how the connectivity and architecture of the cortex are related to the functions of neurones in that area? This will be investigated by imaging the surface of the visual cortex of anaesthetised cats and monkeys as special visual patterns are shown to the eye/s. The overall picture gained of the active and inactive cortical areas will be related to the properties of neurones in those areas and to those of individual input and output fibres. An optical imaging equipment will be acquired in 2004 using a recently awarded LIEF grant to the CI.Read moreRead less
Functional pathways in primate retina. When light enters the eye, specialised nerve cells called photoreceptors transform the light signal into nerve signals. These signals are processed in the retina by two groups of neurones, bipolar and ganglion cells before being sent to higher brain centres. Bipolar and ganglion cells can be subdivided into several types. We will measure which types communicate with each other and which proteins (neurotransmitter receptors) are involved at the site of commu ....Functional pathways in primate retina. When light enters the eye, specialised nerve cells called photoreceptors transform the light signal into nerve signals. These signals are processed in the retina by two groups of neurones, bipolar and ganglion cells before being sent to higher brain centres. Bipolar and ganglion cells can be subdivided into several types. We will measure which types communicate with each other and which proteins (neurotransmitter receptors) are involved at the site of communication between these nerve cells. This study will improve our knowledge of the basis of functional subspecialisation at the earliest stages of the visual process.Read moreRead less
The role of the Supplementary Motor Area in time processing. The neural bases of timing mechanisms (0.1-100s range) are the subject of much debate. We hypothesise that the Supplementary Motor Area (SMA), a major cortical structure involving important dopaminergic pathways, subtends duration encoding, in the way depicted by the 'accumulator model'. Using transcranial magnetic stimulation (TMS) over the SMA, we will test healthy subjects in motor and perceptual timing tasks, compared to Parkinson' ....The role of the Supplementary Motor Area in time processing. The neural bases of timing mechanisms (0.1-100s range) are the subject of much debate. We hypothesise that the Supplementary Motor Area (SMA), a major cortical structure involving important dopaminergic pathways, subtends duration encoding, in the way depicted by the 'accumulator model'. Using transcranial magnetic stimulation (TMS) over the SMA, we will test healthy subjects in motor and perceptual timing tasks, compared to Parkinson's disease patients whose timing performance is impaired due to dopaminergic dysfunction. We expect TMS inhibitory effects to induce predictable performance trends, providing support for the accumulator model and the key role of the SMA in timing.Read moreRead less
Conductance states of a brain glutamine transporter. Brain transporters are the target for many neuroactive drugs that are used to treat anxiety, depression and other psychotic disorders. Transport processes are also targeted to deliver neurotransmitter precursors to the brain to treat disorders such as Parkinson's disease. In this project we will study a transport process crucial for the function of neurons that release glutamate and GABA (gamma-aminobutyric acid) as neurotransmitters. The stud ....Conductance states of a brain glutamine transporter. Brain transporters are the target for many neuroactive drugs that are used to treat anxiety, depression and other psychotic disorders. Transport processes are also targeted to deliver neurotransmitter precursors to the brain to treat disorders such as Parkinson's disease. In this project we will study a transport process crucial for the function of neurons that release glutamate and GABA (gamma-aminobutyric acid) as neurotransmitters. The study of this transport process will be important for understanding disorders like epilepsy and other disorders affecting neuronal excitability.Read moreRead less
Bioinformatics network for the interrogation of adult stem cells. This project addresses the National Research Priority 'Frontier Technologies for Building and Transforming Australian Industries'. The use of state of the art DNA sequencing results in huge amounts of data that is hard to interpret without the use of computers. This project builds Australia's capacity to deal with huge biological datasets by creating software and expertise in handling these datasets. The application of this softwa ....Bioinformatics network for the interrogation of adult stem cells. This project addresses the National Research Priority 'Frontier Technologies for Building and Transforming Australian Industries'. The use of state of the art DNA sequencing results in huge amounts of data that is hard to interpret without the use of computers. This project builds Australia's capacity to deal with huge biological datasets by creating software and expertise in handling these datasets. The application of this software and expertise to our stem cell population in Parkinson's disease patients will enable new insight into the difference between patients and controls.Read moreRead less
Intracortical inhibition evaluated by paired-pulse TMS during choice and simple reaction time tasks. The research will investigate the neurophysiological processes responsible for the selection and initiation of movement in response to an external stimulus. Slowness in the initiation and execution of movement is a common feature of 'neurological aging', neurodegenerative disease, and brain injury. Understanding the brain mechanisms involved in response selection and movement initiation will pro ....Intracortical inhibition evaluated by paired-pulse TMS during choice and simple reaction time tasks. The research will investigate the neurophysiological processes responsible for the selection and initiation of movement in response to an external stimulus. Slowness in the initiation and execution of movement is a common feature of 'neurological aging', neurodegenerative disease, and brain injury. Understanding the brain mechanisms involved in response selection and movement initiation will provide information for the development of specific intervention techniques to improve motor function in these groups.Read moreRead less
How does Motor Cortex Excitability Influence Internal Model Retention. Each year 40,000 Australians suffer from stroke with many survivors left with problems that limit limb function. With reduced duration of hospital care, the opportunities for retraining in the period immediate following stroke are rapidly diminishing. Effective and efficient strategies of rehabilitation that will maximise the level of recovery following stroke will result in benefits expressed in terms of enhanced quality of ....How does Motor Cortex Excitability Influence Internal Model Retention. Each year 40,000 Australians suffer from stroke with many survivors left with problems that limit limb function. With reduced duration of hospital care, the opportunities for retraining in the period immediate following stroke are rapidly diminishing. Effective and efficient strategies of rehabilitation that will maximise the level of recovery following stroke will result in benefits expressed in terms of enhanced quality of life and functional life-span, as well as significantly reduced costs of health care. In understanding the fundamental principles underlying the stability and adaptability of movement coordination, this research is likely to make a significant contribution to the design of programs for rehabilitation of the upper limb.Read moreRead less
Visuomotor Adaptation and Stimulus Response Compatibility: Basic Mechanisms and Safety Implications for Heavy Equipment. This project will explore mechanisms of human visuomotor adaptation using a directional stimulus-response compatibility (SRC) paradigm. The latter refers to the greatly enhanced performance for ?natural? pairings of control movement directions and system output directions. The outcomes are both theoretical (understanding basic processes) and applied (design and training gui ....Visuomotor Adaptation and Stimulus Response Compatibility: Basic Mechanisms and Safety Implications for Heavy Equipment. This project will explore mechanisms of human visuomotor adaptation using a directional stimulus-response compatibility (SRC) paradigm. The latter refers to the greatly enhanced performance for ?natural? pairings of control movement directions and system output directions. The outcomes are both theoretical (understanding basic processes) and applied (design and training guidelines for equipment in construction, mining, transport and aerospace industries). The issue is also significant both theoretically, since models of adaptation and SRC phenomena have not previously been combined, and practically, as serious heavy equipment accidents can result from designs that are not based on sound human performance principles.Read moreRead less