For years, it has been observed through electrophysiological, pharmacological, and molecular studies that levels of adenosine released from glia in the basal forebrain are closely aligned to episodes of sleep and wakefulness. In brief, adenosine levels rise across wakefulness, due, in part, to increased demands for ATP, and dissipate during sleep. This temporal profile of adenosine expression can also be interrupted by sleep loss which prevents adenosine levels from falling at night.

ResearchBlogging.orgIn this week’s Journal of Neuroscience, neuroscientists used adenosine biosensors, which would provide better temporal resolution of changes in adenosine across wakefulness and sleep than previously conventional methods like microdialysis. They also undertook electrophysiological studies to examine changes in adenosine receptor-mediated suppression of excitatory transmission, which is another common characteristic of adenosine (it suppresses cholinergic signaling in order to enhance sleepiness). Third, they compared these adenosine-related effects found in wild-type mice with those in transgenic mice that have impaired exocytotic release of adenosine at the level of SNARE complexes on glia.

As hypothesized, the researchers found that adenosine levels and adenosine-mediated excitatory signaling deriving from the hippocampus increased during wakefulness, dissipated during sleep, and continued to rise with sleep loss. This temporal (and rhythmic) profile has severely attentuated in the SNARE-mutated mice demonstrating that glial complexes are extremely important for adenosine-mediated transmission and subsequent effects on behavior, in this case, on sleep and wake and related memory encoding processes.


Schmitt, L., Sims, R., Dale, N., & Haydon, P. (2012). Wakefulness Affects Synaptic and Network Activity by Increasing Extracellular Astrocyte-Derived Adenosine Journal of Neuroscience, 32 (13), 4417-4425 DOI: 10.1523/JNEUROSCI.5689-11.2012