Chapter 9 Sleep and Biological Rhythms

Stages of sleep ► Most sleep research conducted in a sleep laboratory ► Attaches electrodes to measure EEG, EMG (electromyogram; to measure muscle activity), and EOG (electro-oculogram; to measure eye movements) ► EEG stages  Awake ► Alpha activity – smooth electrical activity of 8-12 Hz recorded from the brain; state of relaxation ► Beta activity – irregular electrical activity of Hz recorded from the brain; state of arousal  Stage 1 sleep ► Transition b/t sleep and wakefulness ► Theta activity – EEG activity of Hz that occurs intermittently during early stages of slow-wave sleep and REM sleep

Stages of sleep ► EEG stages  Stage 2 sleep ► EEG is generally irregular but contains periods of theta activity, sleep spindles and K complexes ► Some experimenters believe that sleep spindles represent the activity of a mechanism that is involved in keeping a person asleep  Stage 3 & 4 sleep ► Delta activity – regular, synchronous electrical activity of less than 4 Hz recorded from the brain; occurs during the deepest stages of slow-wave sleep  REM sleep – a period of desynchronized EEG activity during sleep, at which time dreaming, rapid eye movements, and muscular paralysis occur ► Dreaming during this state; tend to be narrative in form  Stages 1-4 referred to as non-REM sleep  Stages 3-4 referred to as slow-wave sleep  During rest of the night subject will alternate b/t periods of non-REM sleep and REM sleep, each cycle about 90 min long, containing ~20-30 min of REM sleep

Stages of sleep ► The fact that REM sleep occurs at regular 90-minute intervals suggests that a brain mechanism alternately causes REM and slow-wave sleep ► The cyclic nature of REM sleep appears to be controlled by a “clock” in the brain that also controls an activity cycle that continues through waking ► Basic rest-activity cycle – a 90-mn cycle (in humans) of waxing and waning alertness; controlled by a biological clock in the caudal brain stem; controls cycles of REM sleep and slow-wave sleep ► REM sleep also includes lack of muscle tonus, penile erection or vaginal secretion

Mental activity during sleep ► Cerebral blood flow in the human brain during REM sleep is high in the visual association cortex but low in the inferior frontal cortex (concerned with planning, strategies) ► Eye movements during REM sleep may be related to the visual imagery that occurs while we dream ► Particular brain mechanisms that become active during a dream are those that would become active if the events in the dream were actually occurring

Disorders of sleep ► Insomnia  Affects ~20% of pop  One of the most important causes of insomnia is sleeping medication, because of developed tolerance and withdrawal symptoms ► Drug dependency insomnia – caused by the side effects of ever-increasing doss of sleeping medications  Unreliability of self-reports; sleep studies help doctors prescribe correctly  Sleep apnea – cessation of breathing while sleeping; mostly caused by an obstruction of the airway that can be corrected surgically or by a breathing mask ► Narcolepsy  Characterized by periods of irresistible sleep, attacks of cataplexy (complete paralysis that occurs during waking), sleep paralysis (paralysis occurring before falling asleep), and hypnagogic hallucinations (vivid dreams that occur just before a person falls asleep)  Produced by a brain abnormality that disrupts the neural mechanisms that control various aspects of sleep and arousal

Disorders of sleep ► Narcolepsy con’t  Human narcolepsy is a genetic disorder that is influenced by unknown env’tal factors  There is a mutation of the gene that codes for a receptor for the peptide hypocretin (aka orexin), which is produced by neurons in the hypothalamus ► REM sleep behavior disorder  A neurological disorder in which the person does not become paralyzed during REM sleep and thus acts out dreams  Appears to be a neurodegenerative disorder with at least some genetic component

Why do we sleep? ► Functions of slow-wave sleep  Researchers believe the primary function of slow-wave sleep is to permit the brain to rest  Essential for survival (even seen in species where it would seem dangerous to sleep)  Effects of sleep deprivation ► Sleep deprivation has not been shown to be necessary for the body to function properly ► However, cognitive functions are affected ► Fatal familial insomnia – characterized by progressive insomnia, results in damage to the thalamus ► Lab rats forced to remain awake eat more, but lose weight (due to increased metabolism) and eventually die  Effects of exercise on sleep ► No changes in slow-wave or REM sleep in subjects on bed-rest

Why do we sleep? ► Functions of slow-wave sleep con’t  Effects of mental activity on sleep ► Increased mental activity causes subjects to experience increased slow-wave (especially Stage 4) sleep ► Functions of REM sleep  After several days of REM sleep deprivation, subjects would show a rebound phenomenon (increase of normal percentage of REM sleep) when permitted to sleep normally  The highest proportion of REM sleep is seen during the most active phase of brain development ► So why do adults have REM sleep then? ► Maybe to facilitate modest brain changes due to learning  Studies with lab animals demonstrate that REM sleep does indeed facilitate learning  In humans, learning can affect the amount of REM sleep a person obtains

Chemical control of sleep ► Since sleep is regulated, the body must either produce a sleep- promoting substance or a wakefulness-promoting substance ► Suggested that adenosine may play a role in the control of sleep, by increasing the amount of delta activity during sleep ► Neural control of arousal  Acetylcholine ► ACh antagonists decrease EEG signs of cortical arousal while agonists increase them ► Activation of cerebral cortex and increased release of ACh stimulated by a group of ACh neurons located in basal forebrain  Norepinephrine ► Locus coeruleus – a dark-colored group of NE cell bodies located in the pons near the rostral end of the floor of the 4 th ventricle; involved in arousal and vigilance ► NE increases an animal’s ability to pay attention to stimuli in the env’t

Activity of NE neurons in LC

Chemical control of sleep ► Neural control of arousal con’t  Serotonin ► Most of the brain’s 5-HT neurons are located in raphe nuclei, which is located in the medullary and pontine regiond of the reticular formation ► Stimulation of the neurons causes locomotion and cortical arousal ► 5-HT neurons in raphe nuclei activated highly during awake states, and less during deep stages of sleep

5-HT neurons in raphe nuclei

Activity of 5-HT neurons in raphe nuclei

Chemical control of sleep  Histamine ► Cell bodies of histaminergic neurons located in tuberomammillary nucleus of the hypothalamus ► Project to cerebral cortex, and increase cortical activation and arousal  Hypocretin ► Cell bodies of neurons that secrete hypocretin are located in the lateral hypothalamus and terminate in several regions involved in arousal ► Has an excitatory, wakefulness-promoting effect

Chemical control of sleep ► Neural control of slow-wave sleep  One region important: ventrolateral preoptic area (VLPA), rostral to the hypothalamus; destruction of this area produced total insomnia in rats  Contains inhibitory GABA-secreting neurons and these neurons send their axons to the tuberomammillary nucleus, dorsal pons, raphe nuclei, and locus coeruleus  Also receives inhibitory info from these regions, creating a flip-flop effect of either awake or sleep states ► Neural control of REM sleep  In lab animals, REM sleep also creates PGO waves (pons, genicultae, occipital) in addition to EEG activity, muscular paralysis, etc  PGO waves are bursts of phasic electrical activity originating in the pons followed by activity in the LGN and visual cortex  REM sleep controlled by mechanisms located within the pons: ► The executive mechanism  ACh neurons located in dorsolateral pons (peribrachial area) trigger the onset of REM sleep

Chemical control of sleep ► Neural control of REM sleep (con’t)  The executive mechanism ► Activation of single neurons in this area are related to the sleep cycle ► Axons of these neurons project to the reticular formation, forebrain, brain stem regions that control eye movements ► Carbachol, an ACh receptor agonist, when infused into the reticular formation, produces REM sleep in lab animals ► Magnocellular nucleus – locaed in the medulla; involved in the muscular paralysis during REM sleep  5-HT and NE ► Activity of neurons in the dorsal raphe nucleus and locus coeruleus normally inhibits REM sleep and a reduction in firing rate may trigger a bout of REM sleep

Biological clocks ► Daily rhythms in behavior and physiological processes called circadian rhythms; some are passive responses to changes in illumination, while others are controlled by mechanisms within the organism ► 24 hour period for plants and animals ► Zeitgeber – a stimulus (usually the light of dawn) that resets the biological clock that is responsible for circadian rhythms ► Superchiasmatic nucleus – situated atop the optic chiasm; contains a biological clock that is responsible for organizing many of the body’s rhythms  activity, drinking, hormonal secretion, sleep cycles, feeding  Receive projections from the retina (retinohypothalamic pathway)  Photoreceptors provide SCN with info about light levels (via use of the chemical melanopsin)  SCN also receives light info from Intergeniculate leaflet (part of the LGN)  Neurons of the SCN project to the midbrain, hypothalamic nuclei and others in order to control eating, drinking, sleep cycles, and hormone secretion

Biological clocks ► SCN contains a biological clock ► Evidence suggests that each neuron in the SCN contains a “clock” ► Clock “ticking” is provided by the production and breakdown of a protein that acts back on the genes responsible for their own production; thus creating a cycle

Control of seasonal rhythms ► The pineal gland and melatonin  Pineal gland – sits on top of the midbrain; produces melatonin and plays a role in circadian and seasonal rhythms  Melatonin is secreted at night and controls hormones, physiological processes and behaviors that show seasonal variations (e.g. hibernation)

Changes in circadian rhythms ► Shift work and jet lag  When people abruptly change their daily rhythms of activity, their internal circadian rhythms become desynchronized with those in the external env’t  E.g. jet lag