Adenosine and the homeostatic control of sleep
Supported by the Wellcome Trust
We all experience the effects of sleep homeostasis: if we are deprived of sleep, we spend much longer time asleep when this is possible. One simple explanation for sleep homeostasis is that during wakefulness a sleep promoting substance (somnogen) accumulates. When sleep occurs, the somnogen disappears. During prolonged waking more of the somnogen accumulates and consequently it takes longer to dissipate during sleep and hence a longer period of sleep ensues. Technically this is known as rebound sleep.
Adenosine is now known as a somnogen and is a key mediator of rebound sleep and sleep homeostasis. Strong evidence shows that during prolonged waking adenosine accumulates in an area of the brain known as the basal forebrain. This enhanced accumulation is responsible for greater periods of subsequent sleep. During rebound sleep the levels of adenosine in the basal forebrain diminish. Despite this well established role of adenosine in the control of sleep, we still do not understand why adenosine should accumulate during wakefulness and dissipate during sleep.
Banner illustration: left panel, coronal diagram of the pre optic areas of the rat brain; middle panel, coronal brain slice (cut in half down midline) corresponding to the diagram left with biosensors in place in cortex and HDB/MCPO (basal forebrain); right panel, release of adenosine and inosine in the basal forebrain following stimulation with NMDA with simultaneous whole cell recording from BF neuron.