Wakefulness acetylcholine

Some arousal-related neurotransmitters, including noradrenaline, serotonin, and acetylcholine, feed back to inhibit POA sleep-active neurons. This aspect of the system has been reviewed previously (McGinty Szymusiak, 2000 Saper et al., 2001). Therefore, once sleep-active neurons are activated, arousal-related neurons are inhibited, and inhibitory control of sleep-active neurons by arousal systems is reduced. In this way, sleep onset is facilitated. That is, the mutually inhibitory systems can switch more quickly from wake to sleep, and back. These mutually inhibitory interactions also promote stability of both waking and sleep. 

The concept of chemical neurotransmission originated in the 1920s with the classic experiments of Otto Loewi (which were themselves inspired by a dream), who demonstrated that by transferring the ventricular fluid of a stimulated frog heart onto an unstimulated frog heart he could reproduce the effects of a (parasympathetic) nerve stimulus on the unstimulated heart (Loewi Navratil, 1926). Subsequently, it was found that acetylcholine was the neurotransmitter released from these parasympathetic nerve fibers. As well as playing a critical role in synaptic transmission in the autonomic nervous system and at vertebrate neuromuscular junctions (Dale, 1935), acetylcholine plays a central role in the control of wakefulness and REM sleep. Some have even gone as far as to call acetylcholine a neurotransmitter correlate of consciousness (Perry et al., 1999). 

The development of antibodies against ChAT allowed the distribution of neurons producing acetylcholine in the nervous system to be revealed (Mesulam et al., 1983 Armstrong et al., 1983 Jones Beaudet, 1987 Vincent Reiner, 1987). In the context of control of wakefulness and REM sleep two groups of cholinergic neurons are of primary importance. Neurons located in the basal forebrain and medial septum provide the cholinergic innervation of the cerebral... 

Steriade, M. (2004). Acetylcholine systems and rhythmic activities during the waking - sleep cycle. Prog. Brain Res. 145, 179-6. 

Jouvet, M. (1972). The role of monoamines and acetylcholine-containing neurons in the regulation of the sleep-waking cycle. Ergeb. Physiol. 64, 166-307. 

Acetylcholine modulates sleep and wakefulness a synaptic perspective... 

The neural structures involved in the promotion of the waking (W) state are located in the (1) brainstem [dorsal raphe nucleus (DRN), median raphe nucleus (MRN), locus coeruleus (LC), laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT), and medial-pontine reticular formation (mPRF)] (2) hypothalamus [tuberomammillary nucleus (TMN) and lateral hypothalamus (LH)[ (3) basal forebrain (BFB) (medial septal area, nucleus basalis of Meynert) and (4) midbrain ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) (Pace-Schott Hobson, 2002 Jones, 2003). The following neurotransmitters function to promote W (1) acetylcholine (ACh LDT/PPT, BFB) (2) noradrenaline (NA LC) (3) serotonin (5-HT DRN, MRN) (4) histamine (HA TMN) (5) glutamate (GLU mPRF, BFB, thalamus) (6) orexin (OX LH) and (7) dopamine (DA VTA, SNc) (Zoltoski et al, 1999 Monti, 2004). 

Marrosu, F., Portas, C., Mascia, M. S. et al. (1995). Microdialysis measurement of cortical and hippocampal acetylcholine release during the sleep-wake cycle in freely moving cats. Brain Res. 671, 329-32. 

Vazquez, J., Lydic, R. Baghdoyan, H. A. (2002). The nitric oxide synthase inhibitor NG-Nitro-L-arginine increases basal forebrain acetylcholine release during sleep and wakefulness. J. Neurosci. 22, 5597-605. 

Intracerebroventricular infusion of CST-14 dramatically increases the amount of slow wave activity in rats, at the expense of wakefulness. The mechanism by which CST-14 enhances cortical synchronization has been established through the interaction of CST-14 with acetylcholine, a neurotransmitter known to be involved in the maintenance of cortical desynchronization. Application of acetylcholine (ACh) in the anesthetized animal increases fast activity, and this effect is blocked with the simultaneous addition of CST-14. These data suggest that CST-14 increases slow wave sleep by antagonizing the effects of ACh on cortical excitability. In addition to this mechanism, cortistatin may enhance cortical... 

Wake G, Court J, Pickering A, Lewis R, Wilkins R and Perry E (2000). CNS acetylcholine receptor activity in European medicinal plants traditionally used to improve failing memory. Journal of Ethnopharmacology, 69, 105-114. 

Dopamine has an alerting effect. Neurochemicals involved in wakefulness include norepinephrine and acetylcholine in the cortex and histamine and neuropeptides (e.g., substance P and corticotropin-releasing factor) in the hypothalamus. 

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