Quantification of whole brain structural connectivity and fibre densities. The project is intended to develop and improve accuracy in tools used to measure brain connections. Its overall aim is to produce definitive evidence of the biological accuracy of quantitative measures of brain structural connectivity as derived from diffusion magnetic resonance imaging (MRI). Discovery in the quantitative field of MRI research is important to worldwide efforts to identify the human ‘connectome’. The proj ....Quantification of whole brain structural connectivity and fibre densities. The project is intended to develop and improve accuracy in tools used to measure brain connections. Its overall aim is to produce definitive evidence of the biological accuracy of quantitative measures of brain structural connectivity as derived from diffusion magnetic resonance imaging (MRI). Discovery in the quantitative field of MRI research is important to worldwide efforts to identify the human ‘connectome’. The project plans to bring together novel diffusion MRI post-processing methods and state-of-the-art 3-D glass-brain histology techniques using mice. Investment in MRI research that specifically addresses methods to accurately measure structural brain connectivity may ultimately contribute to improving non-invasive imaging methods.Read moreRead less
Biophysics-informed deep learning framework for magnetic resonance imaging. This project aims to bring about a paradigm shift from the conventional non-quantitative magnetic resonance imaging to ultra-fast, quantitative, and artefact free imaging. This project integrates biophysics and artificial intelligence, and it is expected to bring new knowledge in both fields. The expected outcomes of this project include next generation magnetic resonance imaging methods with a fundamental shift in the ....Biophysics-informed deep learning framework for magnetic resonance imaging. This project aims to bring about a paradigm shift from the conventional non-quantitative magnetic resonance imaging to ultra-fast, quantitative, and artefact free imaging. This project integrates biophysics and artificial intelligence, and it is expected to bring new knowledge in both fields. The expected outcomes of this project include next generation magnetic resonance imaging methods with a fundamental shift in the approach to image artefacts and image quantification. This project is expected to advance both single subject and population level biomedical imaging with greater accuracy and cost-effectiveness. This project also promotes explainable and generalisable artificial intelligence in medical imaging.Read moreRead less
Computational neuroanatomy: analysis of neural connections in the primate brain. This project will map the full network of connections between brain cells, using a computer graphics database that will consolidate data from hundreds of experiments. This will allow the first realistic simulations of neural activity, and will provide new insights about the structure and function of the nervous system.
How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understandi ....How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understanding the dynamics of developmental systems that shape complex brain traits includes establishing new developmental paradigms in evolutionary theory, generating new tools to investigate and manipulate brain gene expression in vivo, and the potential discovery of the causes of neurodevelopmental dysfunction.Read moreRead less
The processing of sensory information within cortical circuits. This project aims to improve our knowledge of neuronal activity during sensory perception and therefore shed light on overall brain function during behaviour. Understanding how dendrites receive and process this information is crucial to understanding brain function during sensory processing and perception. This proposal aims to characterise dendritic activity during sensory input and discover how this activity contributes to behavi ....The processing of sensory information within cortical circuits. This project aims to improve our knowledge of neuronal activity during sensory perception and therefore shed light on overall brain function during behaviour. Understanding how dendrites receive and process this information is crucial to understanding brain function during sensory processing and perception. This proposal aims to characterise dendritic activity during sensory input and discover how this activity contributes to behavioural tasks. In particular, the project plans to investigate activity of different dendritic domains during sensory perception and sensory-based behaviour. The project seeks to improve our knowledge of the importance of dendrites in transforming information from the sensory environment and highlight the cellular and network mechanisms contributing to behaviour.Read moreRead less
Molecular neurobiology of the GABAB receptor: Studies of heteromeric receptor function and signalling. The G protein-coupled receptor (GPCR) for the inhibitory transmitter gamma- aminobutyric acid (GABA) is a unique heterodimer. Molecular analyses will be undertaken to provide insights into its signalling mechanisms and functional regulation. Investigations employing point mutant and chimeric receptors will analyse how ligand binding to the extracellular domain of the GABA-BR1 subunit triggers ....Molecular neurobiology of the GABAB receptor: Studies of heteromeric receptor function and signalling. The G protein-coupled receptor (GPCR) for the inhibitory transmitter gamma- aminobutyric acid (GABA) is a unique heterodimer. Molecular analyses will be undertaken to provide insights into its signalling mechanisms and functional regulation. Investigations employing point mutant and chimeric receptors will analyse how ligand binding to the extracellular domain of the GABA-BR1 subunit triggers G protein-coupling to the intracellular portion of the GABA-BR2 subunit. Focus will be on different modes of GPCR signalling, including constitutive activity and roles for membrane and cytosolic regulatory proteins. Targeted studies of GABAB receptor subunits will provide new information on the mechanistic regulation of GPCR signalling.Read moreRead less
Functional tracing of brain circuitry by a novel approach. A genetically modified virus is taken up by axon terminals (the 'output' part of a nerve cell) and transported by the cell back to the cell body (its 'input' part). Once there, it makes a protein that makes the cell sensitive to blue light. This new tool may be instrumental in answering questions about nerve connections that cannot be answered in other ways.
Subcellular recruitment of a RhoA ubiquitination complex by Rnd proteins. This study addresses a novel molecular mechanism through which members of the Rnd family of GTP-binding proteins regulate the morphology and migration of immature nerve cells of the developing nervous system. This study has broad implications for the understanding of cell migration during embryo development, as well as in health and disease.
The cortical location of hunger and thirst: a multifunctional study in sheep. The escalating problems associated with obesity are immense. These effects contribute to a global epidemic that now eclipses both infectious diseases and (ironically) undernutrition in its proportions. The effects of disorders of thirst are less apparent but potentially devastating albeit on a smaller scale. The elderly and psychotic in the community have impaired thirst mechanisms which impacts on their life in a dra ....The cortical location of hunger and thirst: a multifunctional study in sheep. The escalating problems associated with obesity are immense. These effects contribute to a global epidemic that now eclipses both infectious diseases and (ironically) undernutrition in its proportions. The effects of disorders of thirst are less apparent but potentially devastating albeit on a smaller scale. The elderly and psychotic in the community have impaired thirst mechanisms which impacts on their life in a dramatic way particularly during prolonged hot weather. The aims of these experiments are to understand the basic brain mechanisms that underpin these drives. This understanding will have far reaching repercussions for the community both in terms of promoting good health and in preventative health care.
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Chromatic Inputs to Cortical Receptive Fields in Primates. The human eye contains three kinds of receptors for daytime vision, named blue, green and red cones for their sensitivity to different regions of the visible spectrum. It is known that blue cones contribute to brain pathways for colour vision, but recent data suggest there is also 'cross-talk' of blue cone signals to pathways for motion and high-acuity vision. This project comprises precise measurement of blue cone signals, and anatomica ....Chromatic Inputs to Cortical Receptive Fields in Primates. The human eye contains three kinds of receptors for daytime vision, named blue, green and red cones for their sensitivity to different regions of the visible spectrum. It is known that blue cones contribute to brain pathways for colour vision, but recent data suggest there is also 'cross-talk' of blue cone signals to pathways for motion and high-acuity vision. This project comprises precise measurement of blue cone signals, and anatomical tracing of blue cone pathways, in a primate model for human vision. The data will improve our basic knowledge of how the brain processes sensory signals.Read moreRead less