Brain consists of two basic cell types – neurons and glia. However, the study of glia in brain function has traditionally been neglected in favor of their more “illustrious” counter-parts – neurons that are classed as the computational units of the brain. Glia have usually been classed as “brain glue” - a supportive matrix on which neurons grow and function. However, recent evidence suggests that glia are more than passive “glue” and actually modulate neuronal function. This has lead to the proposal of a “tripartite synapse”, which recognizes pre- and postsynaptic neuronal elements and glia as a unit.However, what is still lacking is rudimentary information on how these cells actually function in situ. Here we propose taking a “bottom-up” approach, by identifying the molecules (and interactions) that control glial function in situ. This is complicated by the fact that glia show profound changes when placed into culture. To circumvent this, we will use recently developed cell sorting techniques, to rapidly isolate genetically marked glial cells from brain – which can then be analyzed using advanced biochemical and physiological techniques. The long-term aim is to identify proteins that can be “tagged” using transgenic technologies to allow protein function to be studied in real-time in vivo, using sophisticated imaging techniques. Given the number of proteins that may be identified we envisage developing new methods of generating transgenic animals that provide an attractive alternative to current “state-of-the art” technology.The importance of studying glial function is given by the fact that every major brain pathology shows reactive gliosis. In the time it takes to read this abstract, 5 people in the EU will have suffered a stroke – not to mention those who suffer other forms of neurotrauma. Thus, understanding glial function is not only critical to understanding normal brain function, but also for relieving the burden of severe neurological injury and disease