The Glial Perspective on Sleep and Circadian Rhythms

Abstract

While neurons and circuits are almost unequivocally considered to be the computational units and actuators of behavior, a complete understanding of the nervous system must incorporate glial cells. Far beyond a copious but passive substrate, glial influence is inextricable from neuronal physiology, whether during developmental guidance and synaptic shaping or through the trophic support, neurotransmitter and ion homeostasis, cytokine signaling and immune function, and debris engulfment contributions that this class provides throughout an organism's life. With such essential functions, among a growing literature of nuanced roles, it follows that glia are consequential to behavior in adult animals, with novel genetic tools allowing for the investigation of these phenomena in living organisms. We discuss here the relevance of glia for maintaining circadian rhythms and also for serving functions of sleep.

Keywords: circadian rhythms; glia; sleep.

Figure 1:

Fly and mammalian glial class influences on sleep behavior and correlates of the state. Behavioral points refer to genes and processes whose manipulation in glia produces changes in sleep amount or quality. Correlates refer to cellular and molecular aspects of glial cells, which have been observed to change as a function of sleep-wake state.

Figure 2:

Astrocytic influence on neuronal clocks and behavioral output. (a) In mammals, astrocytic clocks of the suprachiasmatic nucleus (SCN) influence neuronal clocks via γ aminobutyric acid (GABA) in cell culture and glutamate in vivo. Both populations have rhythmic Ca²⁺ levels, which are antiphasic to each other throughout the day. Other signals such as extracellular ATP, which depends on astrocytic Ca²⁺, might also act to influence neuronal clocks. Neuronal clocks can entrain astrocytic clocks by unknown mechanisms. (b) In flies, disruption of astrocytic vesicular trafficking, as well as enzymes such as ebony and certain transporters and receptors, produces deficits in behavioral output without affecting the core clock in neurons. Some manipulations eliminate rhythms of the pigment dispersing factor (PDF) or expression of the circadian gene PDP1ε, while others act independently. Knockout of the clock in glia has not been shown to affect neuronal clocks, and it is unknown whether neuronal clocks entrain glial ones.