ADVANCED REVIEW Regulation of rhythmic behaviors by astrocytes F. Rob Jackson 1 | Samantha You 1 | Lauren B. Crowe 1 1 Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts Correspondence F. Rob Jackson, Department of Neuroscience, Tufts University School of Medicine, Boston, MA. Email: rob.jackson@tufts.edu Present address Lauren B. Crowe, Department of Biology, Tufts University, Medford, MA Funding information National Institute of Neurological Disorders and Stroke, Grant/Award Numbers: NIH R21 NS107804, P30NS047243; Tufts University School of Medicine Abstract Glial astrocytes of vertebrates and invertebrates are important modulators of nervous system development, physiology, and behavior. In all species examined, astrocytes of the adult brain contain conserved circadian clocks, and multiple studies have shown that these glial cells participate in the regulation of circa- dian behavior and sleep. This short review summarizes recent work, using fruit fly (Drosophila) and mouse models, that document participation of astrocytes and their endogenous circadian clocks in the control of rhythmic behavior. This article is categorized under: Gene Expression and Transcriptional Hierarchies > Regulatory Mechanisms Nervous System Development > Flies KEYWORDS astrocytes, circadian behavior, Drosophila, glia, mouse, sleep 1 | INTRODUCTION There is remarkable conservation of the mechanisms controlling daily rhythms in animal physiology and behavior (Young, 2018). In species ranging from insects to humans, endogenous clocks (circadian clocks) of similar molecular composition regulate daily rhythms in gene expression, metabolism, physiology, and behaviors such as locomotor activ- ity and sleep. Not surprisingly, the circadian control of such processes is vital for survival. Although circadian clocks reside in neural and peripheral tissues of animals, the clock within the brain is most critical for the control of rhythmic behavior. Whereas the neurons participating in circadian control have been the subject of many reviews, the role of glial cells, in particular astrocytes, has received much less attention. This short review will summarize evidence from recent studies using Drosophila and mammalian models that demonstrate participation of glial astrocytes in the control of rhythmic behavior. As background for this review, it is important to note that the properties of circadian activity rhythms and sleep are remarkably similar in Drosophila and mammalian species. Both flies and mammals possess molecular clocks within neural cells, built around PERIOD (PER), a canonical clock protein. Both types of species exhibit daily rhythms in loco- motor activity that can be synchronized to light–dark cycles and persist in constant environmental conditions (e.g., constant dark and temperature). In addition, the organization of fly sleep and wakefulness resembles that of mam- mals. In flies and mammalian species, including humans, there is dual control of sleep by circadian and homeostatic mechanisms. Regulation of sleep by circadian mechanisms is well documented in vertebrates and invertebrates (Dubowy & Sehgal, 2017; Fisher, Foster, & Peirson, 2013), and similar to vertebrates, sleep pressure in flies (e.g., sleep deprivation) initiates a homeostatic response, resulting in recovery sleep. Indeed, a recent publication describes a Dro- sophila gene that appears to specifically regulate sleep homeostasis (Toda, Williams, Gulledge, & Sehgal, 2019). For a more detailed comparison of sleep states in flies and mammals, readers should refer to recent reviews on the topic (Allada, Cirelli, & Sehgal, 2017; Donlea, 2017). Received: 9 September 2019 Revised: 19 November 2019 Accepted: 28 November 2019 DOI: 10.1002/wdev.372 WIREs Dev Biol. 2019;e372. wires.wiley.com/devbio © 2019 Wiley Periodicals, Inc. 1 of 8 https://doi.org/10.1002/wdev.372