Towards direct imaging of neuronal currents with MRI. This project aims to develop novel neuronal current magnetic resonance imaging (nc-MRI) methods that harness the oscillatory behaviour of neuronal magnetic fields. Current methods of detecting neuronal activity in the living human brain have limited spatial and temporal resolution. Use of nc-MRI aims to overcome these limitations by imaging the effects on the MRI signal of small transient magnetic fields associated with neuronal activity. Sig ....Towards direct imaging of neuronal currents with MRI. This project aims to develop novel neuronal current magnetic resonance imaging (nc-MRI) methods that harness the oscillatory behaviour of neuronal magnetic fields. Current methods of detecting neuronal activity in the living human brain have limited spatial and temporal resolution. Use of nc-MRI aims to overcome these limitations by imaging the effects on the MRI signal of small transient magnetic fields associated with neuronal activity. Signal-to-noise ratio is at the limits of detectability using current imaging systems and nc-MRI is yet to be convincingly demonstrated. An integrated framework for simulating nc-MRI in the visual cortex is expected to be developed.Read moreRead less
Control of cellular differentiation in the developing brain. This project aims to understand how mature brain cells form during foetal life. The central hypothesis is that a specific transcription factor family, called NFI, regulates the epigenetic state of the cell, allowing chromatin accessibility and subsequent transcriptional activation and repression to control cellular differentiation. Aims 1 and 2 will investigate how brain cells transition from proliferating progenitor cells to different ....Control of cellular differentiation in the developing brain. This project aims to understand how mature brain cells form during foetal life. The central hypothesis is that a specific transcription factor family, called NFI, regulates the epigenetic state of the cell, allowing chromatin accessibility and subsequent transcriptional activation and repression to control cellular differentiation. Aims 1 and 2 will investigate how brain cells transition from proliferating progenitor cells to differentiated mature cell types. Aim 3 will investigate how differentiation is maintained in the adult brain. Methods used involve genome and chromatin analyses of cells isolated from transgenic mouse models. Outcomes and benefits are substantial knowledge gain applicable to stem cell regulation and brain health.Read moreRead less
Old brain cells perform new tricks to allow life-long learning. In the brain, nerve cells transmit electrical signals more quickly and reliably when they are insulated. The insulating cells undergo small adaptive changes that speed up information transfer during learning, and the faster the electrical signal, the better the learning outcomes. This project aims to understand the signals that direct insulating cells to adapt and support life-long learning. In the longer term, this knowledge may be ....Old brain cells perform new tricks to allow life-long learning. In the brain, nerve cells transmit electrical signals more quickly and reliably when they are insulated. The insulating cells undergo small adaptive changes that speed up information transfer during learning, and the faster the electrical signal, the better the learning outcomes. This project aims to understand the signals that direct insulating cells to adapt and support life-long learning. In the longer term, this knowledge may be used to: develop interventions that improve learning and educational outcomes; counteract age-related memory decline and enable longer work force participation; develop strategies to circumvent the memory loss caused by brain diseases, or improve the design of computer hardware.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
Quiet sleep is for repair, active sleep is for learning. Sleep is thought to achieve many different functions, from brain waste clearance to regulating emotions and perception. Understanding sleep functions in animal models has been difficult because sleep has been typically reduced to a single state. Our discovery of distinct sleep stages in the fruit fly provides a powerful way to study how different conserved sleep functions are regulated. This project will use new strategies for manipulating ....Quiet sleep is for repair, active sleep is for learning. Sleep is thought to achieve many different functions, from brain waste clearance to regulating emotions and perception. Understanding sleep functions in animal models has been difficult because sleep has been typically reduced to a single state. Our discovery of distinct sleep stages in the fruit fly provides a powerful way to study how different conserved sleep functions are regulated. This project will use new strategies for manipulating sleep stages in flies to understand their respective physiology and functions. We will test our hypothesis that different categories of sleep functions have been segregated by evolution into different stages: a quiet stage concerned primarily with brain repair and an active stage important for learning.
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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
Specialized glial cells within the hippocampus of the brain regulate important morphological events in embryonic development. Memories of past experiences, and our ability to learn new information, is processed in a region of the brain called the hippocampus. In order for this to occur, the cells that make up the hippocampus must form correctly during embryonic development. This proposal investigates the cellular and molecular mechanisms regulating hippocampal formation. The national benefit of ....Specialized glial cells within the hippocampus of the brain regulate important morphological events in embryonic development. Memories of past experiences, and our ability to learn new information, is processed in a region of the brain called the hippocampus. In order for this to occur, the cells that make up the hippocampus must form correctly during embryonic development. This proposal investigates the cellular and molecular mechanisms regulating hippocampal formation. The national benefit of this work is to provide basic knowledge about the processes that underlie correct brain formation and function, and to understand what processes are disrupted when the brain fails to function correctly. Such disruptions lead to mental retardation and learning difficulties, and in the aged, an inability to form and store new memories, as occurs in dementia.Read moreRead less