Evidence that wakefulness and REM sleep are controlled by a GABAergic pontine mechanism.

The pontine microinjection of the inhibitory neurotransmitter GABA and its agonist induced prolonged periods of wakefulness in unanesthetized, chronic cats. Conversely, the application of bicuculline, a GABA(A) antagonist, resulted in the occurrence of episodes of rapid eye movement (REM) sleep of long duration. Furthermore, administration of antisense oligonucleotides against glutamic acid decarboxylase (GAD) mRNA into the same area produced a significant decrease in wakefulness and an increase in REM sleep. Microinjections of glycine, another major inhibitory neurotransmitter in the CNS, and its antagonist, strychnine, did not have any effect on the behavioral states of sleep and wakefulness. These data argue forcibly that 1) GABAergic neurons play a pivotal role in determining the occurrence of both wakefulness and REM sleep and 2) the functional sequelea of inhibitory GABA actions within the pontine reticular formation are excitatory directives and/or behaviors.