Adenosine inhibits basal forebrain cholinergic and noncholinergic neurons in vitro

Neuroscience. 2006 Jun 30;140(2):403-13. doi: 10.1016/j.neuroscience.2006.02.010. Epub 2006 Mar 20.


Adenosine has been proposed as a homeostatic "sleep factor" that promotes the transition from waking to sleep by affecting several sleep-wake regulatory systems. In the basal forebrain, adenosine accumulates during wakefulness and, when locally applied, suppresses neuronal activity and promotes sleep. However, the neuronal phenotype mediating these effects is unknown. We used whole-cell patch-clamp recordings in in vitro rat brain slices to investigate the effect of adenosine on identified cholinergic and noncholinergic neurons of the magnocellular preoptic nucleus and substantia innominata. Adenosine (0.5-100 microM) reduced the magnocellular preoptic nucleus and substantia innominata cholinergic neuronal firing rate by activating an inwardly rectifying potassium current that reversed at -82 mV and was blocked by barium (100 microM). Application of the A1 receptor antagonist 8-cyclo-pentyl-theophylline (200 nM) blocked the effects of adenosine. Adenosine was also tested on two groups of electrophysiologically distinct noncholinergic magnocellular preoptic nucleus and substantia innominata neurons. In the first group adenosine, via activation of postsynaptic A1 receptors, reduced spontaneous firing via inhibition of the hyperpolarization-activated cation current. Blocking the H-current with ZD7288 (20 microM) abolished adenosine effects on these neurons. The second group was not affected by adenosine. These results demonstrate that, in the magnocellular preoptic nucleus and substantia innominata region of the basal forebrain, adenosine inhibits both cholinergic neurons and a subset of noncholinergic neurons. Both of these effects occur via postsynaptic A1 receptors, but are mediated downstream by two separate mechanisms.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Adenosine / metabolism*
  • Adenosine / pharmacology
  • Adenosine A1 Receptor Agonists
  • Adenosine A1 Receptor Antagonists
  • Animals
  • Cholinergic Fibers / drug effects
  • Cholinergic Fibers / metabolism*
  • Female
  • Male
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism
  • Preoptic Area / cytology
  • Preoptic Area / drug effects
  • Preoptic Area / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Adenosine A1 / metabolism
  • Sleep / drug effects
  • Sleep / physiology
  • Substantia Innominata / cytology
  • Substantia Innominata / drug effects
  • Substantia Innominata / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Transient Receptor Potential Channels / drug effects
  • Transient Receptor Potential Channels / metabolism


  • Adenosine A1 Receptor Agonists
  • Adenosine A1 Receptor Antagonists
  • Potassium Channels
  • Receptor, Adenosine A1
  • Transient Receptor Potential Channels
  • Adenosine
  • Acetylcholine