Astrocytes and the modulation of sleep

Abstract

Astrocytes are being identified as having multiple roles in sleep. Initially they were shown to modulate the process of sleep homeostasis through the release of adenosine which acts on adenosine A1 receptors (A1R) to promote sleep drive. More recent studies indicate that the astrocyte also plays pivotal, sleep-dependent roles in 'cleaning the brain' during sleep. This work indicates that a glymphatic pathway that critically relies on astrocytic aquaporin 4, is able to flush solutes from the brain and that deficits in this pathway may contribute to Alzheimer's disease. Finally, astrocytes are known to play important metabolic roles and provide energy on demand to neurons through an astrocyte-neuron shuttle. Given that the time course of astrocytic function is orders of magnitude slower than that of the neuron, this non-neuronal cell is perfectly tuned to modulating slow, state-dependent changes in the brain.

Figure 1

Expression of dnSNARE in astrocytes leads to reduced sleep pressure. Cortical EEGs were performed on mice and the power of low frequency delta power (0.5–1.5Hz) was measured in dnSNARE and wild type animals. A) During a baseline day the power of low frequency SWA was less in astrocytic dnSNARE mice than in WT littermates. This differences was accentuated during the recovery period following sleep deprivation (B). These observations show the importance of the astrocyte in modulating this feature of sleep homeostasis. From Halassa et al., 2009

Figure 2

Shorter up-states in astrocytic dnSNARE mice. A) Examples of up and down states in wild type and dnSNARE mice. B) Average upstates from WT and dnSNARE mice. C) Cumulative durations of up-states (left) and down states (rights). From Fellin et al 2009

Figure 3

Summary diagram of the glymphatic pathway. Water is siphoned from a para-arteriole pathway (left) through astrocytic Aquaporin 4 and through convective bulk flow flushes solutes of the interstitial fluid to a paravascular efflux pathway. This pathway of brain cleaning is thought to have elevated activity during sleep. From Illes et al 2012