Wakefulness neurotransmitter

Neurotransmitter and biogenic amine derived from the amino acid histidine synthesized in hypothalamic tuber-omamillary neurons (TMN) to maintain wakefulness, feeding rhythms, energy balance, neuroendocrine autonomic control, and memory functions prominent immu-nomodulator and proinflammatory signal released from mast cells in response to allergic reactions or tissue damage. 

A medication that causes induction of sleep. The majority of currently available hypnotics (for example benzodiazepine receptor agonists) act via potentiating the brain s inhibitory GABAergic systems, in turn reducing the activity of arousal (i.e. wake promoting) neurotransmitter systems. 

There have been many references in this book to the role of neurotransmitters in the control of CNS excitability. It is therefore appropriate, but possibly foolhardy, to see if the two natural extremes of that excitability, namely sleep and waking, can be explained in terms of neurotransmitter activity. Of course, these states are not constant our sleep can be deep or light and, even when we are awake, our attention and vigilance fluctuate, as the reading of these pages will no doubt demonstrate. Also, the fact that we sleep does not mean that our neurotransmitters are inactive this would imply that sleep is a totally passive state, whereas all the evidence suggests that it is an actively induced process, subject to refined physiological control. 

The more synchronised the activity of the cortical neurons, the greater the summation of currents and the larger and slower the EEG wave, as in the sleep pattern (Fig. 22.4). While there are some dissociations between EEG pattern and behavioural states, the EEG offers one way of determining experimentally the pathways (and neurotransmitters) that control arousal and sleep, and can be regarded as an important objective measurement of the cortical correlates of sleep and waking. 

Based on the above aeeount of the neuronal pathways thought to be responsible for the basie sleep-wake cyele, the neurotransmitters that are most likely to be involved in the eyele are those which ... 

This neurotransmitter presents something of a paradox in respect of its role in sleep and waking behaviour, although its importance to both is undoubted. Early experiments... 

Complicated processes govern wakefulness, sleep, and the transitions leading to sleep initiation and maintenance. Although the neurophysiology of sleep is complex, certain neurotransmitters promote sleep and wakefulness in different areas of the central nervous system (CNS). Serotonin is thought to control non-REM sleep, whereas cholinergic and adrenergic transmitters mediate REM sleep. Dopamine, norepinephrine, hypocretin, substance P, and histamine all play a role in wakefulness. Perturbations of various neurotransmitters are responsible for some sleep disorders and explain why various treatment modalities are beneficial. 

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). 

Several neurotransmitters and neuropeptides influence sleep-wakefulness, including REM sleep. Although NA-ergic and ACh-ergic influences have been studied more extensively, other neurotransmitters also play an important role in the modulation of REM sleep (Sakai, 1986 Mallick et al, 1999 Jones, 2005). 

ACh regulates the cortical arousal characteristic of both REM sleep and wakefulness (Semba, 1991, 2000 Sarter Bruno, 1997, 2000). Medial regions of the pontine reticular formation (Figs. 5.2 and 5.7) contribute to regulating both the state of REM sleep and the trait of EEG activation. Within the medial pontine reticular formation, presynaptic cholinergic terminals (Fig. 5.1) that release ACh also are endowed with muscarinic cholinergic receptors (Roth et al, 1996). Autoreceptors are defined as presynaptic receptors that bind the neurotransmitter that is released from the presynaptic terminal (Kalsner, 1990). Autoreceptors provide feedback modulation of transmitter release. Autoreceptor activation... 

The basal forebrain is an important way station in the activation of the cerebral cortex from the reticular activating system. AMPA and NMDA injections into the basal forebrain increase wakefulness and reduce sleep (Cape Jones, 2000 Manfridi et al, 1999), effects that are blocked by AMPA and NMDA receptor antagonists (Manfridi et al, 1999). The excitatory cortical projections of the basal forebrain have long been considered purely cholinergic, but many basal forebrain neurons that project to the cortex are now known to contain Glu, which may function as a co-transmitter or even as the primary excitatory neurotransmitter (Manns et al, 2001). The basal forebrain also affects vigilance via synapses to HCT cells in the lateral hypothalamus some of these synapses are glutamatergic (Henny Jones, 2006). 

Neural structures and neurotransmitters involved in the regulation of sleep and waking in laboratory animals... 

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). 

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... 

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