Gillin_1993_Prog.Brain.Res_98_379

As reviewed here and elsewhere in this symposium, acetylcholine, in conjunction with other neurotransmitter systems, plays a very important role in the regulation of circadian and sleep-wake states. To briefly recapitulate, several current basic concepts about the regulation of sleep-wake states include: (a) REM sleep, or at least its phasic events (eye movements and PGO spikes), are promoted by cholinergic neurons originating within the peribrachial regions [LDT/PPT] (Mitani et al., 1988; Shiromani et al., 1988; Datta et al., 1991; Shouse and Siegel, 1992); (b) REM sleep may be inhibited by noradrenergic and serotonergic neurons in the locus coeruleus and dorsal raphe, respectively (Siegel, 1989; Steriade and McCarley, 1990; Jones, 1991); (c) stages 3 and 4 (Delta) sleep are inhibited by cholinergic terminals from basal forebrain to cortex (Buzsaki et al., 1988) and from LDT/PPT to thalamus (Steriade and McCarley, 1990; Steriade et al., 1991); (d) Delta sleep is modulated by complex serotonergic mechanisms; for example, it is increased by pharmacological antagonists of 5HT2 receptors (Declerck et al., 1987; Dugovic et al., 1989; Benson et al., 1991), although the mechanism and neuroanatomical site at which this effect occurs is unknown. Given the importance of mACHR mediation of components of REM sleep, it is unfortunate that so little is known about the distribution of the various subtypes of mACHRs in brainstem areas which regulate REM sleep. mACHR subtypes have been identified by molecular, biological and pharmacological methods.