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, re sulted in the occurrence of episodes of rapid eye movement (REM) sleep of l ong duration. Furthermore, administration of antisense oligonucleotides aga inst glutamic acid decarboxylase (GAD) mRNA into the same area produced a s ignificant decrease in wakefulness and an increase in REM sleep. Microinjec tions of glycine, another major inhibitory neurotransmitter in the CNS, and its antagonist, strychnine, did not have any effect on the behavioral stat es of sleep and wakefulness. These data argue forcibly that 1) GABAergic ne urons play a pivotal role in determining the occurrence of both wakefulness and REM sleep and 2) the functional sequelea of inhibitory GABA actions wi thin the pontine reticular formation are excitatory directives and/or behav iors.