Activation of Basal Forebrain Astrocytes Induces Wakefulness without Compensatory Changes in Sleep Drive.

Autor: Ingiosi AM; Department of Translational Medicine and Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington 99202., Hayworth CR; Department of Translational Medicine and Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington 99202., Frank MG; Department of Translational Medicine and Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington 99202 marcos.frank@wsu.edu.; Gleason Institute for Neuroscience, Washington State University, Spokane, Washington 99202.; Sleep Performance and Research Center, Washington State University, Spokane, Washington, 99202.
Jazyk: angličtina
Zdroj: The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2023 Aug 09; Vol. 43 (32), pp. 5792-5809. Date of Electronic Publication: 2023 Jul 24.
DOI: 10.1523/JNEUROSCI.0163-23.2023
Abstrakt: Mammalian sleep is regulated by a homeostatic process that increases sleep drive and intensity as a function of prior wake time. Sleep homeostasis has traditionally been thought to be a product of neurons, but recent findings demonstrate that this process is also modulated by glial astrocytes. The precise role of astrocytes in the accumulation and discharge of sleep drive is unknown. We investigated this question by selectively activating basal forebrain (BF) astrocytes using designer receptors exclusively activated by designer drugs (DREADDs) in male and female mice. DREADD activation of the G q -protein-coupled pathway in BF astrocytes produced long and continuous periods of wakefulness that paradoxically did not cause the expected homeostatic response to sleep loss (e.g., increases in sleep time or intensity). Further investigations showed that this was not because of indirect effects of the ligand that activated DREADDs. These findings suggest that the need for sleep is not only driven by wakefulness per se, but also by specific neuronal-glial circuits that are differentially activated in wakefulness. SIGNIFICANCE STATEMENT Sleep drive is controlled by a homeostatic process that increases sleep duration and intensity based on prior time spent awake. Non-neuronal brain cells (e.g., glial astrocytes) influence this homeostatic process, but their precise role is unclear. We used a genetic technique to activate astrocytes in the basal forebrain (BF) of mice, a brain region important for sleep and wake expression and sleep homeostasis. Astroglial activation induced prolonged wakefulness without the expected homeostatic increase in sleep drive (i.e., sleep duration and intensity). These findings indicate that our need to sleep is also driven by non-neuronal cells, and not only by time spent awake.
(Copyright © 2023 the authors.)
Databáze: MEDLINE
Externí odkaz: