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Reticular Formation And Sleep


Reticular Formation And Sleep
Sleep
Sleep is a characteristic of all mammals and is defined behaviourally as a reduced responsiveness to environmental stimuli, and electrophysiologically by specific changes in electroencephalographic (EEG) activity. In addition, there are a number of changes associated with autonomic nervous system (ANS) function.
Normal patterns of sleep are essential for human wellbeing, although it is still unclear why we need to dream.


EEG patterns during states of consciousness and slow-wave sleep
EEG recordings from normal awake subjects at rest show a characteristic high-frequency (13–30 Hz, β activity) low-voltage pattern. This desynchronized activity changes as the subject closes their eyes and becomes drowsy, with the new EEG pattern having a lower frequency (8–13 Hz, α activity) but slightly higher voltage.
This pattern is said to be synchronized and results from the simultaneous firing of many cortical neurones following thalamocortical activity.
EEG studies have revealed that sleep occurs in stages.
·       As the subject falls asleep (stage 1), the EEG is similar to the awake EEG (low-voltage, fast activity).
·   As sleep deepens through stages 2 and 3 to stage 4, the EEG amplitude progressively increases and its frequency falls. Stage 3 and 4 sleep is called collectively slow-wave sleep (SWS) or non-rapid eye movement (non-REM) sleep because the eyes are still.
·       After about 90 minutes of sleep, the EEG changes back to a low-voltage, fast pattern that is indistinguishable from stage 1 non-REM sleep. However, during this phase of sleep there are rapid eye movements. This type of sleep is called rapid eye movement sleep (REM sleep), or paradoxical sleep because although the
EEG is similar to that of an awake person, sleepers are difficult to arouse and muscle tone is absent. Most dreaming occurs during REM sleep, although that which takes place during non-REM sleep is said to have a higher emotional content with less detail.

Reticular Formation And Sleep, EEG patterns during states of consciousness and slow-wave sleep, Neural mechanisms of sleep, Sleep disorders, Obstructive sleep apnoea syndrome, Narcolepsy, Hypersomnia (daytime sleepiness), Management of insomnia, Insomnia

Neural mechanisms of sleep
Sleep is an active process involving a number of neurotransmitter systems.
·   Cholinergic neurones in the ascending reticular activating system project via two pathways: a dorsal route through the medial thalamus and a ventral one through the lateral hypothalamus, basal ganglia and forebrain. Extensive thalamocortical projections provide the basis for widespread changes in cortical cell excitability. Activity in cholinergic neurones lead to an increase in arousal and cortical desynchrony. Activity in this system is also responsible for the pontine – geniculo – occipital (PGO) waves, at the onset of REM sleep.
·    Both noradrenergic neurones in the locus coeruleus and serotoninergic (5-hydroxytryptamine [5-HT]) neurones in the raphé nuclei are involved in controlling the balance between different sleep stages and sleep and arousal.
·     Neurones in the ventrolateral preoptic area (VLPA) send an inhibitory γ-aminobutyric acid (GABA)-mediated input to the locus coeruleus, raphé nuclei and tuberomammillary nucleus. The latter contains histaminergic neurones, which are likely to be the substrate for the sedative effects of antihistamine drugs.
·   Other brain regions implicated in sleep and arousal patterns include the suprachiasmatic nucleus of the hypothalamus.
·       A number of peptides have been identified as being associated with sleep states (e.g. orexins and delta sleep-inducing peptide [DSIP]) and appear to be involved in switching sleep–wake cycles.

Sleep disorders
Insomnia
Insomnia is the most common sleep disorder. It can be defined as the failure to obtain the required amount or quality of sleep to function normally during the day. Primary insomnia supposedly brought about by dysfunction of sleep mechanisms in the brain is rare, but these patients may require treatment with hypnotic drugs. Causes of secondary insomnia include psychiatric disease (especially depression and anxiety disorders), physical disorders, chronic pain, drug misuse (e.g. excessive alcohol, caffeine), and old age.

Management of insomnia
Hypnotics are drugs that promote sleep. They include drugs acting at the benzodiazepine receptor (benzodiazepines and Z-drugs), chloral hydrate, chlormethiazole and barbiturates. Benzodiazepines and the more recent Z-drugs are by far the most widely used hypnotics. They also have anxiolytic, anticonvulsant, muscle relaxant and amnesic actions.
·       All the actions of benzodiazepines are believed to be caused by the enhancement of GABA-mediated inhibition in the CNS. GABAA receptors possess several ‘modulatory’ sites including one for benzodiazepines, which when activated causes a conformational change in the GABA receptor. This increases the affinity of GABA binding and enhances the actions of GABA on the Cl conductance of the neuronal membrane. Any benzodiazepine given at night will induce sleep but a rapidly eliminated drug (e.g. temazepam) is usually preferred to avoid daytime sedation. Adverse effects of benzodiazepines include drowsiness, impaired alertness and ataxia as well as a low-grade dependence after a few weeks’ use. Suddenly stopping the drug may cause a physical withdrawal syndrome (anxiety, insomnia) that may last for weeks.
       Some newer drugs do not have the benzodiazepine structure but are benzodiazepine-receptor agonists. These are the so-called Z-drugs, zopiclone, zolpidem and zaleplon. The Z-drugs have shorter half-lives than the benzodiazepines and are less likely to cause daytime sedation. They have a reduced propensity to tolerance and withdrawal and are becoming increasingly popular for the management of insomnia.
For many cases of insomnia, psychological strategies may be effective alternatives to drugs.

Hypersomnia (daytime sleepiness)
This is a serious but less common complaint than insomnia. Common causes of persistent daytime sleepiness include narcolepsy, obstructive sleep apnoea, drugs (e.g. benzodiazepines, alcohol) and depression (20% have hypersomnia rather than insomnia).

Narcolepsy
Narcolepsy is characterized by irresistible sleep episodes lasting 5–30 minutes during the day, often in association with cataplexy (loss of muscle tone and temporary paralysis) usually provoked by emotion, e.g. laughter, anger, as well as sleep paralysis and hallucinations at the time of going to or waking up from sleep. It has a very strong histocompatibility locus antigen (HLA) association (DR2/DQW1) and, while no pathological abnormalities have been detected in these patients, it is likely that there are abnormalities in the brainstem structures underlying sleep, as there is evidence of short latency REM sleep during normal waking hours. In addition, deficiencies in hypocretins or orexins have recently been described in narcolepsy in some patients. The syndrome has a devastating effect on quality of life, which may be improved by long-term treatment with stimulants, e.g. dexamfeta- mine, methylphenidate and modafinil. Clomipramine is used to treat the cataplexy.

Obstructive sleep apnoea syndrome
This occurs if the upper airway at the back of the throat collapses when the patient breathes during sleep. This reduces the oxygen in the blood, which arouses the patient causing him or her to momentarily awake and prevents a normal sleep pattern. The patient, usually an overweight man, is often unaware of these awakenings, but the disruption to sleep results in daytime sleepiness and impaired daytime performance. It can be treated by weight loss, positive ventilatory support at night and, occasionally, oropharyngeal surgery. If sleep apnoea is not treated it can lead to long-term cardiorespiratory problems such as pulmonary hypertension and right heart failure. It is also known that sleep apnoea can have a central nervous system origin.