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Glia: emerging from the shadows

For the past century, the nervous system has been divided into active and passive elements. The active elements, the neurons, have drawn the lion’s share of attention from researchers. Our understanding of how they operate, their connections and how they remember information is reasonably (albeit not fully) well developed. By contrast, we know relatively little about the ‘passive’ elements, the glia. Although first evident in early drawings by Ramon y Cajal, glia have largely evaded the attention of researchers. Apart from studies suggesting roles for them as supporting elements, little was known about glia until about 20 years ago when reports began ascribing various roles for these cells in regulating neuronal excitability and controlling synaptic strength. Since these seminal papers, interest in ‘gliobiology’ has assuredly increased. In the current issue, a number of young investigators who have made seminal findings on glia in the nervous system offer an update on the latest findings. Included among these are updates on the role of glia in the control of cerebrovasculature. Anusha Mishra provides a review of the role of astrocytes in balancing energy demands of neurons with the availability of oxygen and nutrients (Mishra, 2017). Since many of the functional signals in human imaging rely on changes in blood flow, changes in astrocyte function may antecede diagnosis of brain dysfunction based on functional imaging approaches. Nicola Allen and colleagues examine the role of astrocytes in regulating synapses (Blanco-Suárez et al. 2017). Beginning with their role in synaptogenesis and then extending through physiological regulation to a variety of disorders, they provide a detailed and mechanistic overview of astrocyte–synapse function. One of these disorders, epilepsy, is the focus of a review by Christian Henneberger who explains how long-term dysfunction of distinct astrocyte processes such as potassium buffering, gap junction coupling and metabolism may contribute to the pathophysiology of epilepsy (Henneberger, 2017). In addition to astrocytes, the microglia have been the focus of studies examining their role in pathological processes such as inflammation, and also as the brain’s resident ‘gardeners’ that prune synaptic contacts and maintain appropriate neuronal function. Marie-Eve Tremblay and colleagues highlight recent work that showcases our emerging understanding of the key roles played by these cells in brain development, plasticity and cognition (Tay et al. 2017). In addition, they propose a number of important implications for microglia dysfunction in the pathogenesis of multiple brain diseases. Glial cells also play critical roles in the gut. Vladimir Grubišić and Brian Gulbransen highlight many of these in their overview of glia in the enteric nervous system (Grubišić & Gulbransen, 2017). They summarize findings on the role of glia in a diversity of gut functions ranging from motility to epithelial barrier function to inflammation. Understanding the key signalling pathways may provide important targets for therapeutic intervention in gut pathophysiology. This renewed interest in glia is long overdue. One of the reasons for the current surge may be the availability of new tools that allow unprecedented access to the nervous system. These include high resolution imaging tools that, when combined with fluorescent biological reporters, allow investigators a peek into the brain of awake, behaving animals. With the widespread adoption of genetic tools that allow for cell-targeted manipulations to causally link glial function to nervous system physiology, we are now at the cusp of making groundbreaking discoveries regarding the role of these non-neuronal entities in the nervous system. The authors who have contributed these reviews will play a major role in leading this charge and training the next generation of glio-scientists who begin to change our view of how the nervous system works.