THE RAPID EYE MOVEMENT (REM) STAGE OF SLEEP IS CHARACTERIZED BY CORTICAL AND HIPPOCAMPAL ACTIVATION, RAPID EYE MOVEMENTS, SILENCING OF brainstem aminergic neurons, and postural atonia.1 Cholinergic activation

THE RAPID EYE MOVEMENT (REM) STAGE OF SLEEP IS CHARACTERIZED BY CORTICAL AND HIPPOCAMPAL ACTIVATION, RAPID EYE MOVEMENTS, SILENCING OF brainstem aminergic neurons, and postural atonia.1 Cholinergic activation plays an important role in the generation of REM sleep, since pontine microinjections of cholinergic agonists into the pontine reticular formation trigger or enhance a rapid eye movements sleep-like state, whereas antagonists suppress REM sleep,1-7 and endogenous acetylcholine release is increased in the pons in association with REM sleep.8 The localization of the site or sites at which REM sleep-like phenomena are elicited most effectively is important for advancing our understanding of the neurochemistry and neurophysiology of this stage of sleep. Microinjection studies in cats point to a discrete region in the dorsal pontine tegmentum as the site for the cholinergic triggering of REM sleep-like state.9-11 REM sleep-like effects, including postural atonia,12-15 REMs,16 and silencing of medullary serotonergic neurons,17 are elicited from this area also in decerebrate cats. In urethane-anesthetized rats, carbachol injections into a homologous pontine site elicit REM sleep-like bouts comprising cortical and hippocampal activation, silencing of pontine noradrenergic neurons, and a profound suppression of activity in hypoglossal (XII) motoneurons.18-19 The loss of upper airway muscle tone is a clinically important feature of REM sleep; in people with anatomically compromised upper airways who are affected by the obstructive sleep apnea syndrome, it is the main reason for sleeprelated upper airway obstructions.20 In two studies in chronically instrumented rats, injections of carbachol into the dorsal pontine tegmentum enhanced a REM sleep-like state or produced some of its phenomena,21,22 but in many other studies in rats, pontine carbachol injections have yielded variable results, often leading to increased amount of wakefulness.23-26 This may be due, in part, to the use of relatively large doses and volumes of the drug that did not allow for a satisfactory spatial resolution of the effective sites. There is also evidence pointing to the ventral pontine tegmentum as the site at which carbachol triggers a REM sleep-like state in chronically instrumented cats.27-29 Ventral carbachol injections also cause hippocampal theta in spontaneously breathing, anesthetized rats,30 and these effects are accompanied by decreased genioglossal muscle activity and increased respiratory rate.31 These results suggest an important role for the ventral pontine tegmentum in the cholinergic activation of REM sleep or some of its components. Carbachol Injections Into the Ventral Pontine Reticular Formation Activate Locus Coeruleus Cells in Urethane-Anesthetized Rats