INVESTIGATION OF A BRAIN RHYTHM. Elucidation of brain function remains a frontier for human discovery. To date, research has largely focussed on brain connectivity with major advances in knowledge of input/output function of brain regions. Yet, there remains little understanding of higher order processes that underlie functions such as mood states and consciousness. Investigation of brain rhythms represent a step to unravelling such processes, as rhythms both act as autonomous clocks and generat ....INVESTIGATION OF A BRAIN RHYTHM. Elucidation of brain function remains a frontier for human discovery. To date, research has largely focussed on brain connectivity with major advances in knowledge of input/output function of brain regions. Yet, there remains little understanding of higher order processes that underlie functions such as mood states and consciousness. Investigation of brain rhythms represent a step to unravelling such processes, as rhythms both act as autonomous clocks and generate synchronised neuronal activity. This project aims to investigate mechanisms underlying a specific class of brain rhythm implicated in control of mood states. Positive outcomes from this basic research may lead to better drug therapies for controlling specific mental disorders.Read moreRead less
Neurological cell replacement therapies: improving outcomes by matching developmental profiles of transplanted cells with the damaged brain area. Stem cell transplantation offers a way to replace nerve cells lost due to acute CNS injury or chronic degenerative conditions such as Parkinson's Disease. However, to date, results have been disappointing because of poor differentiation, survival and integration of stem cells confounded by ethical issues associated with the use of embryos as the source ....Neurological cell replacement therapies: improving outcomes by matching developmental profiles of transplanted cells with the damaged brain area. Stem cell transplantation offers a way to replace nerve cells lost due to acute CNS injury or chronic degenerative conditions such as Parkinson's Disease. However, to date, results have been disappointing because of poor differentiation, survival and integration of stem cells confounded by ethical issues associated with the use of embryos as the source of stem cells. The experiments conducted in this study will provide strategies to improve the efficacy of stem cell transplantation into the damaged CNS as well as developing the use of autologous bone marrow stem cells for repair. Outcomes will be improved transplant methodologies and expertise for the bio-technology industry. Read moreRead less
Central pathways regulating visceral pain. This project aims to investigate the neural pathways within the spinal cord and brain processing colorectal pain perception. The project aims to identify the spinal cord neurons relaying colorectal signalling into the brain and the influence of descending modulation from the brainstem upon these pathways. The outcomes will greatly benefit fundamental understanding of the central pathways processing visceral pain.
Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occul ....Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occult segmental pattern in adult mice. This work will give us a new way of understanding the organisation of brainstem centres that control breathing, cardiovascular functions and emotional states.Read moreRead less
How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information i ....How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information is essential to understand how blood pressure is controlled under healthy conditions.Read moreRead less
Molecular control of adult neural stem cell quiescence. The objective of this project is to improve our understanding of adult neural stem cell biology and function. Within the central nervous system of the brain, neural stem cells persist throughout adult life. These cells continually produce new neurons that are pivotal for processes including learning and memory, and deficits in adult neurogenesis have been linked to age-related cognitive decline. Adult neural stem cells are predominantly qui ....Molecular control of adult neural stem cell quiescence. The objective of this project is to improve our understanding of adult neural stem cell biology and function. Within the central nervous system of the brain, neural stem cells persist throughout adult life. These cells continually produce new neurons that are pivotal for processes including learning and memory, and deficits in adult neurogenesis have been linked to age-related cognitive decline. Adult neural stem cells are predominantly quiescent, dividing rarely to ensure that they are not prematurely exhausted. However, the factors that maintain this quiescence are very poorly defined. The project aims to understand how stem cell quiescence is controlled at both a molecular and cellular level in vivo within the adult mouse brain.Read moreRead less
Transcriptional regulation of brain size during development. This project aims to understand the fundamental mechanisms through which intermediate progenitor cell (IPC) formation is regulated within the cerebral cortex. The cerebral cortex plays a key role in functions central to our existence, including emotion, behaviour, learning and memory. During development, cortical neural stem cells produce neurons via IPCs. This project expects to discover the genetic programs regulating neuronal produc ....Transcriptional regulation of brain size during development. This project aims to understand the fundamental mechanisms through which intermediate progenitor cell (IPC) formation is regulated within the cerebral cortex. The cerebral cortex plays a key role in functions central to our existence, including emotion, behaviour, learning and memory. During development, cortical neural stem cells produce neurons via IPCs. This project expects to discover the genetic programs regulating neuronal production, providing significant conceptual advances in this key field. This will provide significant benefits, such as enhancing our understanding of how overall brain size is regulated during development.Read moreRead less
Understanding the mechanisms of GABA type-A receptor activation and drug modulation. There is currently little understanding of how sedative and anxiolytic drugs, including valium, interact with their receptors in the brain. This project will dramatically increase our understanding of how these receptors work and how drugs affect their activity. This will provide new insights into drug discovery and design.
Early formation of the preplate establishes the cerebral cortex. The cerebral cortex is arguably the most complex area of the brain due to its ability to process and integrate a wide variety of information in a seamless manner. To understand how this occurs, it is essential to understand how the cerebral cortex is built during embryonic life. The focus of this project is on the formation of the very earliest neurons of the cortex, called preplate neurons. This project aims to: test a new model f ....Early formation of the preplate establishes the cerebral cortex. The cerebral cortex is arguably the most complex area of the brain due to its ability to process and integrate a wide variety of information in a seamless manner. To understand how this occurs, it is essential to understand how the cerebral cortex is built during embryonic life. The focus of this project is on the formation of the very earliest neurons of the cortex, called preplate neurons. This project aims to: test a new model for preplate development with regards to their origin; their function in formation of the cerebral cortex; and the the molecular mechanisms underlying their development. This work provides a developmental framework for understanding how the cerebral cortex is established.Read moreRead less
Characterisation of monoaminergic transmission in Central Amygdala. This project will identify the distribution and function of dopamine, serotonin and noradrenalin receptors on the various cell types and their inputs, in the medial, lateral and capsular divisions of Central Amygdala (CeA). We will test for tonic endogenous activation of monoaminergic receptors and synaptic release from electrically stimulated fibers terminating in CeA. Using paired recordings and calcium imaging, we will invest ....Characterisation of monoaminergic transmission in Central Amygdala. This project will identify the distribution and function of dopamine, serotonin and noradrenalin receptors on the various cell types and their inputs, in the medial, lateral and capsular divisions of Central Amygdala (CeA). We will test for tonic endogenous activation of monoaminergic receptors and synaptic release from electrically stimulated fibers terminating in CeA. Using paired recordings and calcium imaging, we will investigate intracellular mechanisms underlying monoamine receptor mediated effects. These findings when correlated with published behavioural studies will provide greater understanding of the role of the divisions of CeA and the inputs they receive, in the function of the amygdala.Read moreRead less