The impact of female sex hormones on neurodevelopment. This project aims to characterise the contribution of sex hormones to the development of emotional brain circuits in female adolescents. Puberty is associated with profound changes in emotional behaviours in females, but we know little about the underlying brain mechanisms. In particular, research has neglected to consider the role of the sex hormones for which changes are a defining feature of female puberty (eg, oestradiol). This work will ....The impact of female sex hormones on neurodevelopment. This project aims to characterise the contribution of sex hormones to the development of emotional brain circuits in female adolescents. Puberty is associated with profound changes in emotional behaviours in females, but we know little about the underlying brain mechanisms. In particular, research has neglected to consider the role of the sex hormones for which changes are a defining feature of female puberty (eg, oestradiol). This work will be the first to comprehensively advance our understanding of the unique role of sex hormones in shaping the adolescent female brain. It will provide critical understanding of how individual differences in hormonal factors increase risk for emotional problems in females, and inform treatment strategies.Read moreRead less
Understanding the generation of hypothalamic sleep neurons. This Project aims to investigate the mechanisms controlling the formation of the sleep neurons in the hypothalamus. We all sleep, and normal sleep-wake cycles play a central role in our biology. The functional role of these sleep neurons in the mature brain are well established. However, how the neurons are generated during development is very poorly defined. This project aims to address this critical knowledge gap, and will greatly inc ....Understanding the generation of hypothalamic sleep neurons. This Project aims to investigate the mechanisms controlling the formation of the sleep neurons in the hypothalamus. We all sleep, and normal sleep-wake cycles play a central role in our biology. The functional role of these sleep neurons in the mature brain are well established. However, how the neurons are generated during development is very poorly defined. This project aims to address this critical knowledge gap, and will greatly increase our understanding of how the development of this critical aspect of organismal function is orchestrated during development. This project will also develop bioinformatics tools with broad utility within the biosciences field and enhance the capacity for interdisciplinary international collaborations.Read moreRead less
Hippocampal regulation of goal-directed decision-making. The hippocampus is a part of the brain that is central to learning and memory yet little is known about its role in decision-making. It is the aim of this application to provide the first detailed, causal evidence of hippocampal regulation of decision-making. This is significant because many mental health disorders and dementias that involve decision-making deficits are characterised by hippocampal dysfunction, but any direct link between ....Hippocampal regulation of goal-directed decision-making. The hippocampus is a part of the brain that is central to learning and memory yet little is known about its role in decision-making. It is the aim of this application to provide the first detailed, causal evidence of hippocampal regulation of decision-making. This is significant because many mental health disorders and dementias that involve decision-making deficits are characterised by hippocampal dysfunction, but any direct link between these factors is unknown. The outcomes of the current grant will provide the first evidence of that link, thus providing deeper understanding of the neurophysiological mechanisms of these disorders, which could eventuate in the creation of more beneficial treatments. Read moreRead less
Novel dopamine pathways underlying motivated behaviours. Rewards such as food, sex and social media are seeked on daily basis. Neurological and psychological basis of learning and memory of reward processing behaviour. This project maps real time neural activity during reward processing in two novel brain regions. It has the potential to revolutionize the understanding of the brain mechanisms in reward processing. The biological data obtained can be directly integrated into computational modelli ....Novel dopamine pathways underlying motivated behaviours. Rewards such as food, sex and social media are seeked on daily basis. Neurological and psychological basis of learning and memory of reward processing behaviour. This project maps real time neural activity during reward processing in two novel brain regions. It has the potential to revolutionize the understanding of the brain mechanisms in reward processing. The biological data obtained can be directly integrated into computational modelling approaches to benefit reward processing algorithms for learning behaviours in humans or artificial intelligence. This project will fuel the understanding of algorithms driving social media platforms and consumer consumption, hence driving economic and technological progress in Australia.Read moreRead less
Investigating the role of Zona Incerta RXFP3+ cells in learning and memory. Learning and memory are fundamental to human and animal behaviour. We identified a specific population of cells in the zona incerta of the brain, where activation inhibits expression of memory, and facilitates the acquisition of new learning. Aside from our observations, nothing is currently known about the anatomy and function of these cells. This project aims to map how they connect to the rest of the brain, to observe ....Investigating the role of Zona Incerta RXFP3+ cells in learning and memory. Learning and memory are fundamental to human and animal behaviour. We identified a specific population of cells in the zona incerta of the brain, where activation inhibits expression of memory, and facilitates the acquisition of new learning. Aside from our observations, nothing is currently known about the anatomy and function of these cells. This project aims to map how they connect to the rest of the brain, to observe how these connections are recruited during learning and memory, and then to test their function experimentally. The outcomes will extend the known neural circuitry that controls learning by defining how and where these unexplored pathways fit within it; thus advancing knowledge regarding neural regulation of behaviour.
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Hunger flexibly modifies hypothalamic neural circuits responding to threat. Animal and human behaviour frequently involves a choice between actions or goals with conflicting positive and negative outcomes. However, the appropriate action or goal in conflicting situations often depends on physiological pressures like hunger, stress and mating opportunities. For example, the need for resources within an environment, such as food, drives approach behaviour, whereas threats to survival, such as pred ....Hunger flexibly modifies hypothalamic neural circuits responding to threat. Animal and human behaviour frequently involves a choice between actions or goals with conflicting positive and negative outcomes. However, the appropriate action or goal in conflicting situations often depends on physiological pressures like hunger, stress and mating opportunities. For example, the need for resources within an environment, such as food, drives approach behaviour, whereas threats to survival, such as predator cues, enhance avoidance behaviour. This project will uncover the neural circuitry and endocrine mechanisms through which hunger influences hypothalamic threat-detecting circuits that suppress food intake. These studies provide a new hypothalamic model to understand risk/reward decision in the brain.Read moreRead less
Imaging the human cerebellum during motor learning and timing. The cerebellum has long fascinated scientists for its remarkable anatomy and physiology and the critical role that it plays in motor function, and more recently for its more general functions of cognition and emotion. Developments in non-invasive imaging of cerebellar activity have opened up exiting new opportunities to probe its wider functioning. We aim to further develop these new methods in order to facilitate their availability ....Imaging the human cerebellum during motor learning and timing. The cerebellum has long fascinated scientists for its remarkable anatomy and physiology and the critical role that it plays in motor function, and more recently for its more general functions of cognition and emotion. Developments in non-invasive imaging of cerebellar activity have opened up exiting new opportunities to probe its wider functioning. We aim to further develop these new methods in order to facilitate their availability to the wider research community, and to demonstrate their utility by application to the role of the cerebellum in learning and timing. The outcomes of this work will be of considerable benefit to a wide range of scientists and clinicians who will be able to make use of the new methods for their own research.Read moreRead less
Platform technology to decode motor control through ultra high-field MRI. This project aims to advance our understanding of the poorly understood neural circuits that enable fine motor control in humans. To obtain this knowledge, new platform technology will be developed to capture the full kinematics of the hand during concurrent functional magnetic resonance imaging at ultra high-field. This device will allow testing of fundamental theories describing the canonical microcircuits involved in ha ....Platform technology to decode motor control through ultra high-field MRI. This project aims to advance our understanding of the poorly understood neural circuits that enable fine motor control in humans. To obtain this knowledge, new platform technology will be developed to capture the full kinematics of the hand during concurrent functional magnetic resonance imaging at ultra high-field. This device will allow testing of fundamental theories describing the canonical microcircuits involved in hand motion. Expected outcomes include new evidence of mirror neurons and observation of predictive error signals in the motor cortex. This new knowledge paves the way towards improved computer-brain interface technology which is likely to create benefits through translation to applications such as artificial limb control.Read moreRead less
Beyond Neuroinflammation: The Role of Microglia in Synaptic Plasticity. Microglia are the immune cells of the brain and are known to respond to infectious and non-infectious insults to the nervous system. This project aims to use the transparent and genetically amenable brain of the zebrafish, to explore new functions of microglia at the single cell level in the intact, behaving animal, through visualization of cellular components of the brain (neurons, glia, microglia, blood vessels, synapses), ....Beyond Neuroinflammation: The Role of Microglia in Synaptic Plasticity. Microglia are the immune cells of the brain and are known to respond to infectious and non-infectious insults to the nervous system. This project aims to use the transparent and genetically amenable brain of the zebrafish, to explore new functions of microglia at the single cell level in the intact, behaving animal, through visualization of cellular components of the brain (neurons, glia, microglia, blood vessels, synapses), and through the genetic manipulation of synaptic density, and real time observation of microglia in the process.Read moreRead less
Integrative brain imaging technologies. This project aims to develop quantitative metabolic imaging using simultaneous magnetic resonance imaging (MRI) and positron emission tomography (PET). The current generation of MR-PET scanners are capable of simultaneously acquiring MRI and PET data to enable quantitative anatomical, physiological and metabolic imaging. The project aims to develop new MRI methods for quantitative anatomical mapping, MR-based motion correction of dynamic PET scan data, and ....Integrative brain imaging technologies. This project aims to develop quantitative metabolic imaging using simultaneous magnetic resonance imaging (MRI) and positron emission tomography (PET). The current generation of MR-PET scanners are capable of simultaneously acquiring MRI and PET data to enable quantitative anatomical, physiological and metabolic imaging. The project aims to develop new MRI methods for quantitative anatomical mapping, MR-based motion correction of dynamic PET scan data, and joint estimation of physiological and metabolic organ activity. These advances will create innovative imaging technologies for advanced biomedical imaging research with a particular emphasis in healthy ageing.
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