Nitric oxide modulates the discharge rate of basal forebrain neurons

During prolonged wakefulness, the concentrations of nitric oxide (NO) and adenosine (AD) increase in the basal forebrain (BF). AD inhibits neuronal activity via adenosine (A1) receptors, thus providing a potential mechanism for sleep facilitation. Although NO in the BF increases adenosine and promotes sleep, it is not clear whether the sleep promotion by NO is mediated through adenosine increase, or NO independently of adenosine could modulate sleep.

The objective of the study was to clarify whether NO modulates the discharge rate of BF neurons and whether this effect is mediated via AD.

We measured the discharge rates of BF neurons in anesthetized rats during microdialysis infusion of NO donor alone or in combination with A1 receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine.

NO dose dependently modulated the discharge rate of BF neurons. NO donor (0.5 mM) increased the discharge rates in 48% of neurons and decreased it in 22%. A 1-mM dose decreased it in 55% and increased in 18%. Tactile stimulus affected the discharge rates of most neurons: 60% increased (stimulus-on) it and 14% decreased it (stimulus-off). A 1-mM NO donor predominantly inhibited neurons of both stimulus related types. A small proportion of stimulus-on (23%) neurons but none of the stimulus-off neurons were activated by NO donor. The blockade of A1 receptors partly prevented the inhibitory effect of NO on most of the neurons. This response was more prominent in stimulus-on than in stimulus-off neurons.

NO modulates the BF neuronal discharge rates in a dose-dependent manner. The inhibitory effect is partly mediated via adenosine A1 receptors.