The spinal cord and the brainstem contain the cells necessary for life-supporting functions. However, how these cells contribute to such functions is largely unknown.
This project will investigate the properties of cells controlling essential functions such as blood pressure and heart rate regulation.
Manipulating the activity of these cells with drugs or electrical stimulation is currently under investigation for several different therapies e.g. vagal nerve stimulation to treat heart failure. This project will inform such work. It will also examine how the generation of new cells (neural stem cells), even in adulthood, can influence existing nerve cell circuits, as well as probing the mechanisms controlling them.
Manipulating the production and/or differentiation of neural stem cells created inside an organism holds promise for future therapies for conditions such as spinal cord injury, motor neurone diseases and multiple sclerosis.
Plan of work and impact of our studies
Spinal cord and brainstem will be obtained from terminally anaesthetised rats and mice. Tissue will be preserved using chemicals, then sectioned and stained to reveal cells and their connections. In other experiments, tissue will not be chemically treated, but will be sectioned to incubate in a bath to keep cells alive to allow their functions to be investigated.
In some experiments specific cells will be labelled with a dye prior to tissue preparation. This will be done by either using mice genetically altered so that specific cell types express a reporter molecule that can be monitored, or by conducting surgical procedures several days or weeks prior to tissue preparation in which tracing compounds will be applied to nerves, organs or the central nervous system.
The majority of the procedures will require removal of tissue following terminal anaesthesia. For surgical procedures, animals will be anaesthetised during the surgery and receive post-operative pain relief as required.
Following the recovery period, animals will be terminally anaesthetised for tissue retrieval. Tissue from one animal will be maximally utilised – for example, to stain for different cell types in alternate sections or to use different cultured slices in multiple tests.
Modulating the activity of the nervous system by direct electrical or chemical intervention is increasingly under investigation for treatments of disorders such as hypertension, heart failure and multiple sclerosis.
However, knowledge of the neuronal circuitry underlying such modulation is far from complete and furthering such understanding is likely to contribute to development of more targeted and better treatments. Recent technological advances in imaging and manipulating specific cell types have improved the ability to gain this understanding and these will be applied in this project.
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