The basal forebrain is a wakefulness-promoting area, where three types of neurons (the cholinergic, GABAergic and glutamatrgic) send their projections to the cortex, and through the activity of these projections, increase cortical activity.


Adenosine, the core molecule of ATP, acts also as a neurotransmitter: through A1 receptors it inhibits neuronal activity. Increase in extracellular adenosine concentration in the basal forebrain decreases the activity of the cortically-projecting neurons thus promoting sleep. We have proposed that prolonged neuronal activity during prolonged wakefulness increases extracellular adenosine through excessive consumption of ATP. This would be a short negative feed-back loop from energy consumption to decreased neuronal activity.

nitric oxide (no)

Nitric oxide is a gaseous neurotransmitter, which increases adenosine in neuronal cultures. We found that without exception, nitric oxide and adenosine concentrations increased/decreased in the basal forebrain together. NO is metabolized by three different enzymes: neuronal, epithelial and inducible. With a series of experiments we showed that NO during sleep restriction is solely increased by the iducible synthase. This was rather surprising, since this metabolic pathway is normally activated only as a part of the innate immune defense.

basal forebrain (BF)

Basal forebrain turned out to be a very specific structure. Surprisigly, we were not able to measure adenosine increases in any other waking-promoting nuclei, suggesting that the BF cortically-projecting neurons would have a specific role in regulation of sleep homeostasis.

cholinergic lesion

The role of the three types of cortically-projecting neurons was studied using a specific lesion of the cholinergic cells. This lesion completely prevented in crease in both adenosine and nitric oxide (and also lactate), as well as increase in sleep (measured as duration of NREM and EEG delta power) after sleep restriction.

WE also studied the hypothesis that energy depletion in the basal forebrain can induce excesssive sleep, resembling that induced by prolonged wakefulness. We showed that indeed, a local, experimentally induced energy depletion increased sleep as well as extracellular adenosine levels. These results suggested that a local energy depletion in the BF could be an essential component of sleep homeostasis regulation.


Aging is accompanied by many sleep problems. We studied the potential disturbance in regulation of sleep homeostasis and found that adenosine-, nitric oxide- and lactate levels increase less in old than in young as responste to sleep restriction .