Endogenous and exogenous nitric oxide in the pedunculopontine tegmentum induces sleep

Mesopontine cholinergic cells in the pedunculopontine tegmental (PPT) nuclei modulate the control of the wake-sleep cycle by releasing acetylcholine to their target structures. These cells also synthesize nitric oxide (NO) which diffuses into the extracellular space and acts as a neuronal messenger. The present study is based on the hypothesis that NO synthesis and its presence in the extracellular space in the PPT play a functional role in regulating the behavioral states of waking and sleep. This hypothesis was tested by microinjecting a control vehicle, NO donor, S-Nitroso-N-acetylpenicillamine (SNAP) and a competitive inhibitor of NO synthase enzyme (NOS), N(G)-Nitro-L-arginine methylester hydrochloride (L-NAME) into the PPT while quantifying the effects on wakefulness and sleep. Six cats were implanted with bilateral guide tubes for PPT microinjection and with standard electrodes to measure waking, slow-wave sleep (SWS), and rapid eye movement (REM) sleep. Five-hour free-moving polygraphic recordings were made following each microinjection (0.25 microl) of control saline, SNAP or L-NAME. Following microinjection of SNAP into the cholinergic cell compartments of the PPT, SWS and REM sleep were increased by 41.65% and 72.10% respectively, compared to the control microinjection. Microinjection of L-NAME reduced SWS and REM sleep by 40.33% and 62.05%, respectively, compared to controls. The present results demonstrate that endogenous NO synthesized within the PPT cholinergic cells functions as a paracrine signal in the control of waking and sleep by modulating local cholinergic cells.