Regulation of rhythmic behaviors by astrocytes

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F. Rob Jackson, Samantha You, Lauren B. Crowe

Published Online: Dec 15 2019

DOI: 10.1002/wdev.372

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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 circadian 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

Clock protein cycling in flies and mice. (a) PERIOD (PER) localization in neurons and glia of the adult fly brain. Locations of PER‐containing neurons are circled. (b) Rhythm of PER abundance in glia of the fly optic lobe. Glial PER abundance is highest between ZT21 and ZT1. Abbreviations: Pr, protocerebrum; OL, optic lobe. Ng, Tangredi, & Jackson, and unpublished. (c) Luciferase (luc) signal in astrocytes of the suprachiasmatic nuclei (SCN) 96 hr after infection with AAV2/10‐Bmal1::luc virus. (d) Rhythm of Bmal1::luc signal in SCN astrocytes. Unpublished Bmal1‐::luc results were kindly provided by Erik Herzog and Chak Foon Tso (Washington University, St. Louis, MO)

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Astrocyte regulation of sleep by secreted factors. (a) Circuits regulating sleep homeostasis and wakefulness are modulated by astrocyte‐derived adenosine (Ado) or D‐serine, respectively. ATP is secreted from mammalian astrocytes via SNARE‐dependent mechanisms and converted to Ado which acts on AdoA1R to regulate sleep homeostasis. Ado commonly acts on presynaptic A1 receptors to regulate neurotransmitter release, although it can act on postsynaptic receptors also. D‐serine is a coagonist that most likely acts on postsynaptic NMDA receptors. Although the sources of D‐serine are controversial (Ivanov & Mothet, ), evidence suggests that astrocytic D‐serine is important for wakefulness and released via vesicular mechanisms (Papouin, Dunphy, Tolman, Dineley, & Haydon, ). (b) Modulation of a hypothetical sleep circuit by Noktochor (NKT) or Eiger (EGR), postulated to be secreted from astrocytes to regulate sleep. They are depicted here as acting postsynaptically, but they might regulate sleep via a presynaptic action. Fly EGR is thought to bind to its receptor (Wengen) to modulate sleep. Similarly, secreted Fly NKT may act in a receptor‐dependent manner to promote sleep, although its receptor has not yet been identified. Although it is likely that NKT and EGR are secreted from vesicles, this has not been documented experimentally. (c) Punctate localization of an NKT:GFP fusion in astrocyte processes of the fly optic lobe. Green, GFP signal; Red, nuclei of astrocytes. M, optic medulla. (d) Nkt knockdown in astrocytes reduces night sleep without affecting day sleep. ZT0, lights on; ZT12, lights off. Orange line, knockdown flies; green and black lines, control flies

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