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
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
Development of novel reagents that specifically counteract EphA4 to enhance axonal regeneration. This project will examine the role of EphA4, an important guidance protein, in neural cell regeneration. The goal is to understand the signalling mechanisms that inhibit regeneration in the central nervous system and to develop novel biological agents to overcome these processes and promote functional recovery after nervous system injury or disease.
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
Neural migration: Which cells advance and which stay behind? This project aims to examine the neural crest cells that colonise the developing gut and to identify why some cells advance while others stay behind to populate a region. Directed cell migration is essential for normal development, including for the nervous system. In most of the migratory cell populations that have been analysed to date, all of the cells migrate as a collective from one location to another. However, there are also mi ....Neural migration: Which cells advance and which stay behind? This project aims to examine the neural crest cells that colonise the developing gut and to identify why some cells advance while others stay behind to populate a region. Directed cell migration is essential for normal development, including for the nervous system. In most of the migratory cell populations that have been analysed to date, all of the cells migrate as a collective from one location to another. However, there are also migratory cell populations that must populate the areas through which they migrate, and thus some cells get left behind while others advance. The planned data are likely to be relevant to other cell populations that also populate the areas through which they migrate, including neural crest-derived melanocytes and Schwann cell precursors.Read moreRead less
Electrical activity in early enteric neuron development. Intestinal movements and secretion are critical to the good health and nutrition of both humans and animals. These functions are regulated by a large nervous system contained within the intestinal wall, the enteric nervous system. This project will identify how enteric nerve cells develop and how their behaviour influences the development of other enteric nerve cells. This is will provide an important base for more applied research aime ....Electrical activity in early enteric neuron development. Intestinal movements and secretion are critical to the good health and nutrition of both humans and animals. These functions are regulated by a large nervous system contained within the intestinal wall, the enteric nervous system. This project will identify how enteric nerve cells develop and how their behaviour influences the development of other enteric nerve cells. This is will provide an important base for more applied research aimed at developing treatments for diseases like chronic constipation and irritable bowel syndrome. It will also contribute to the growing knowledge about how epigenetic factors can modify genetically programmed development within the nervous system.Read moreRead less
Cell cycle and enteric neuron and glial differentiation. Enteric neurons arise from a very small starting population of precursor (neural crest) cells, most of which emigrate from the hindbrain, and colonise the developing gut. Over a protracted period of time the precursors proliferate and differentiate into glia and many different types of neurons. Cell cycle exit is a critical event in the development of many neuron types, largely because the time at which cells exit from the cell cycle lim ....Cell cycle and enteric neuron and glial differentiation. Enteric neurons arise from a very small starting population of precursor (neural crest) cells, most of which emigrate from the hindbrain, and colonise the developing gut. Over a protracted period of time the precursors proliferate and differentiate into glia and many different types of neurons. Cell cycle exit is a critical event in the development of many neuron types, largely because the time at which cells exit from the cell cycle limits the number of neurons that will be generated. We will determine whether exit from the cell cycle contributes to the differentiation and specification of enteric neurons and glia.Read moreRead less
Cellular bases of enteric neural circuitry underlying gut propulsion. This project aims to investigate the neural bases of behaviour in the mammalian gut. The Enteric Nervous System (ENS) plays a critical role in the propulsion of intestinal contents. This project expects to establish how specific functional classes of enteric neurons control propulsion along the gut. By recording the simultaneous neural activity from hundreds of different functional classes of enteric nerve cells simultaneously ....Cellular bases of enteric neural circuitry underlying gut propulsion. This project aims to investigate the neural bases of behaviour in the mammalian gut. The Enteric Nervous System (ENS) plays a critical role in the propulsion of intestinal contents. This project expects to establish how specific functional classes of enteric neurons control propulsion along the gut. By recording the simultaneous neural activity from hundreds of different functional classes of enteric nerve cells simultaneously, whilst recording intestinal muscle electrical activity and the movements of the gut wall, the project expects to identify which enteric neurochemical classes of neurons generate specific motor patterns along the intestine.Read moreRead less