Glial cell involvement in spinal motor control: cheering from the side-lines or part of the team?

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Research investigating the function of the brain and spinal cord (central nervous system) typically focuses on the role of nerve cells. However, recent work suggests that other cells, called glial cells, also control brain activity and therefore behaviour. Furthermore, the dysfunction of glial cells is known to be involved in many disorders of the central nervous system. Given the potential importance of glial cells in both health and disease, and the lack of widespread acceptance that glial cells are more than just 'support cells', we aim to provide clear evidence of involvement of glial cells in the control of neural networks and ultimately behaviour. We will achieve this by studying the role of glial cells in neural networks of the spinal cord which control movement. We have chosen networks of the spinal cord because, unlike most networks in the brain, they are relatively well-defined and we know and can measure the behaviour they control.Our research will involve the use of state-of-the-art genetic, physiological and imaging techniques that allow us to measure the activity of neurons and glial cells and study their interactions. Using isolated pieces of mouse spinal cord we will first define the mechanisms of bi-directional signalling between glial cells and neurons. We will then examine the effect that glia to neuron signalling has on the network of neurons in the spinal cord which controls walking. This network can be studied using isolated mouse spinal cord tissue which can generate the electrical signals that control walking even when 'in a dish'. Next, we will study glia to neuron signalling in human cells. We will use new technology which allows stem cells to be derived from human skin samples. These stem cells can then be turned into glial cells and spinal neurons which can be grown together and studied in the lab. By defining the ways in which glial cells and neurons of the spinal cord communicate and the effect this signalling has on neural networks that control movement, we will provide important new information about the role of glial cells in the generation of central nervous system activity and ultimately the control of behaviour. In addition, given that many diseases of the brain and spinal cord involve glial cells, the basic knowledge we generate about the function of glial cells (in mice and importantly also humans) will be critical for future studies targeting glial cells to design new treatments for a range of diseases.