Beyond Neurons: The Glue that Holds the Brain Together
When you think about how the brain enables us to sense our surroundings and ponder complex questions, you would most likely consider neurons as the stars of the show. Indeed, much of modern neuroscience aims to understand how different populations of neurons–at a single neuron and network level–drive behaviors and cognition as well as what happens to them in disease. However, what if I told you that neurons only make up a fraction of the diverse and numerous cell types in our brains? Non-neuronal cells, called glia, are just as abundant and have recently taken over the spotlight in the past decade as more research underscores their active role in shaping the nervous system [1,2]. Having their own unique structures and functions, the major types of glial cells in the central nervous system (CNS) include astrocytes, microglia, and oligodendrocytes. Once viewed as solely the “glue” that holds the brain together and maintains CNS homeostasis, glial cells are now becoming acknowledged as key contributors to normal and abnormal brain physiology.
Of the glial cells in the CNS, astrocytes have been increasingly shown to regulate neuronal activity underlying important behaviors. Unlike neurons, astrocytes are electrically non-excitable but they do form interconnected networks to communicate with each other and can respond to neuronal inputs like neurotransmitters and neuromodulators through calcium signaling. Through these calcium dynamics, astrocytes can become activated and mediate brain region-specific processes related to sleep [3,4], attention [5], and spatial learning and memory [6,7]. The ability of astrocytes to not only interact with neurons but also further modulate neural circuits behind distinct behaviors is what makes them well-positioned to be active integrators of brain physiology. However, in response to CNS diseases, injuries, or infections, the role of astrocytes in the brain becomes complicated. Astrocytes undergo “reactive astrogliosis” which is characterized by morphological and physiological changes that affect their normal functions [8]. Interestingly, these changes may have neuroprotective and/or neurotoxic effects, depending on the pathology [9,10]. How and why such differences occur are questions currently being explored across a variety of disease contexts and model systems.
Despite the outstanding questions that remain about astrocytes in health and disease, many of the current discoveries (and future ones) are a direct result of the expanding toolbox of neuroscientists and researchers. More importantly, this is not only the case for research focused on astrocytes but also microglia and oligodendrocytes. In the next decade of neuroscience research, be sure to watch out for how our understanding of glia as active players in the nervous system improves as we discover new exciting things about them.
Reference
[1] Allen, N.J. and Barres, B.A. (2009). Neuroscience: Glia - more than just brain glue. Nature, 457(7230), 675–677
[2] Kottmeier, R. et al. (2020). Wrapping glia regulates neuronal signaling speed and precision in the peripheral nervous system of Drosophila. Nature communications, 11(1), 4491
[3] Bojarskaite, L. et al. (2020). Astrocytic Ca2+ signaling is reduced during sleep and is involved in the regulation of slow wave sleep. Nature communications, 11(1), 3240
[4] Vaidyanathan, T.V. et al. (2021). Cortical astrocytes independently regulate sleep depth and duration via separate GPCR pathways. eLife, 10, e63329
[5] Nagai, J. et al. (2019). Hyperactivity with Disrupted Attention by Activation of an Astrocyte Synaptogenic Cue. Cell, 177(5), 1280–1292.e20
[6] Lee, H.S. et al. (2014). Astrocytes contribute to gamma oscillations and recognition memory. Proceedings of the National Academy of Sciences of the United States of America, 111(32), E3343–E3352
[7] Hösli, L. et al. (2022). Decoupling astrocytes in adult mice impairs synaptic plasticity and spatial learning. Cell reports, 38(10), 110484
[8] Escartin, C. et al. (2021). Reactive astrocyte nomenclature, definitions, and future directions. Nature neuroscience, 24(3), 312–325
[9] Han, R.T. et al. (2021). Astrocyte-immune cell interactions in physiology and pathology. Immunity, 54(2), 211–224
[10] Jiwaji, Z. et al. (2022). Reactive astrocytes acquire neuroprotective as well as deleterious signatures in response to Tau and Aß pathology. Nature communications, 13(1), 135
Edited by Alexandra Fink
