Recent large scale, multi-national research projects have begun to map the connections of the brain. Their goals are similar – to understand how the brain is wired, through building biologically detailed reconstructions and simulations including the rodent, and ultimately, the human brain.
However, a major omission is the spinal cord and the brainstem, despite these regions containing the neuronal circuits necessary for life supporting functions. The aim of our work is to understand the wiring of the brainstem and spinal cord.
We will investigate the properties of cells controlling essential functions such as blood pressure regulation. Manipulating the activity of these cells with drugs or electrical stimulation is currently under investigation for several different therapies eg vagal nerve stimulation to treat heart failure. This project will inform such work.
We will also examine how the generation of new cells (neural stem cells) even in adulthood can influence existing circuits, as well as probing the mechanisms controlling them. Manipulating the production and/or differentiation of endogenous neural stem cells 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 by chemical fixation, sectioned and stained to reveal cells and their connections. In other experiments, tissue will not be fixed and 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 transgenic animals in which specific cell types express a reporter molecule, 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 analgesia 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.
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