Distinct functional states of astrocytes during sleep and wakefulness: Is norepinephrine the master regulator?

Abstract

Astrocytes are the chief supportive cells in the central nervous system, but work over the past 20 years have documented that astrocytes also contribute to complex neural processes, such as working memory. Recent discoveries of norepinephrine-mediated astrocytic Ca2+ responses have raised the possibility that astrocytic activity in the adult brain is driven by global responses to changes in behavioral state. Moreover, analysis of the interstitial space volume suggests that astrocytes may undergo changes in cell volume in response to activation of norepinephrine receptors. This review will focus on what is known about astrocytic functions within the nervous system, and how these functions interrelate with rapid changes in behavioral state mediated by norepinephrine signaling.

Keywords: Astrocytes; Behavioral State; Calcium; Circadian; Homeostasis; Norepinephrine; Potassium; Sleep; State-dependent; Wakefulness.

Conflict of interest statement

Conflict of Interest

John O’Donnell, Fengfei Ding, Maiken Nedergaard have received grants from the National Institutes of Health (NIH).

Figures

Figure 1

Astrocytes are critical support cells of the brain. A) A schematic drawing of astrocytic complexity and coverage of brain vasculature. B) Astrocytes act as the predominate route for clearance of excitatory extracellular glutamate in the nervous system [16]. C) In response to heightened neuronal activity or reduced oxygen tension, astrocytes release PGE2 [68] and potassium [69], stimulating vasodilation. D) During neuronal activity, astrocytes’ rapidly uptake K+ to maintain homeostasis and prevent excessive neuronal depolarization [9].