PSYC326_Chapter 9
Disorders of sleep: narcolepsy
A neurological disorder characterized by sleep (or some of its components) at inappropriate times Sleep attacks Cataplexy Paralysis
Stages of sleep: sleep laboratories
A sleep laboratory: located at a university or medical center, consists of one or several small bedrooms adjacent to an observation room, where the experimenter spends the night The experimenter prepares the sleeper for electrophysiological measurements by attaching electrodes to the scalp to monitor the brain's activity and to the face to monitor muscle activity Other electrodes and transducing devices can be used to monitor autonomic measures such as heart rate, respiration, and changes in the ability of the skin to conduct electricity
Stages of sleep: overview of the cycles
1. Waking - Alpha: 8-12 Hz - Beta: 13-30 Hz 2. Stage 1 - NREM sleep - Theta: 3.5-7.5 Hz 3. Stage 2 - NREM sleep - Sleep spindles - K complexes 4. Stage 3 - Slow wave sleep - Delta activity (<3.5 Hz) 5. REM - REM sleep - Theta and beta activity
Stages of sleep: REM sleep
90 minutes after the beginning of sleep: EEG suddenly becomes mostly desynchronized, with occasional occurrences of theta waves - similar to the record obtained during stage 1 sleep 20-30 minutes Eyes are rapidly moving back and forth beneath closed eyelids Profound loss of muscle tone - Aside from occasional twitching, a person actually becomes paralyzed during REM sleep Brain is very active - Cerebral blood flow and oxygen consumption are accelerated During most periods of REM sleep: male's penis and a female's clitoris will become at least partially erect, and a female's vaginal secretions will increase - Males, genital changes do not signify that the person is experiencing a dream with sexual content Might not react to most noises, but he or she is easily aroused by meaningful stimuli - sound of his or her name When awakened, a person appears alert and attentive Report dreaming when awoken - Dreams tend to be narrative in form, with a storylike progression of events Consolidation of nondeclarative memories
Disorders of sleep: narcolepsy - cataplexy
A cataplectic attack: person will sustain varying amounts of muscle weakness A person can become completely paralyzed and slump down to the floor. The person will lie there, fully conscious, for a few seconds to several minutes - Muscular paralysis occurs at an inappropriate time - Cause: massive inhibition of motor neurons in the spinal cord As in REM sleep, the person continues to breathe and is able to control eye movements
Biological clocks: circadian rhythms - zeitgeber
A cue given by the environment, such as a change in light or temperature, to reset the internal body clock. Light serves as a zeitgeber: it synchronizes the endogenous rhythm. Studies with many species of animals have shown that if they are maintained in constant darkness, a brief period of bright light will reset their internal clock, advancing or slowing it depending on when the light flash occurs - Exposed to bright light soon after dusk: the biological clock is set back to an earlier time - as if dawn had not come yet - Light occurs late at night: the biological clock is set ahead to a later time - as if dawn had already come Using zeitgebers such as clocks or other time cues, individuals who are blind or live in polar regions with extended periods of light or dark easily adapt to a 24-hour environment
Neural control of arousal: acetylcholine (ACh) - agonist and antagonist
Acetylcholinergic agonists: increase EEG signs of cortical arousal Acetylcholinergic antagonists: decrease EEG signs of cortical arousal
Stages of sleep: wavelengths - active awake and quiet awake
Active awake: beta activity - Arousal Quiet awake: alpha activity - Relaxed
Neural control of sleep/wake transitions: role of adenosine in sleep/wake transitions
Adenosine is released by astrocytes when neurons are metabolically active. Accumulation of adenosine --> drowsiness and sleep. Level of adenosine increased during wakefulness and slowly decreased during sleep, especially in the basal forebrain Infusion of an adenosine agonist into the vlPOA: 1) activated neurons in vlPOA, 2) decreased the activity of histaminergic neurons of the tuberomammillary nucleus, and 3) increased slow-wave sleep Adenosine receptors are found on neurons in many regions of the brain - including the orexinergic neurons of the lateral hypothalamus Unlikely that all of the sleep-promoting effects of adenosine involve the neurons of the vlPOA.
Neural control of arousal: overview
Adenosine: sleep promoting - Brain region containing cell bodies: - Waking levels: increase with longer periods of wake - Slow wave sleep levels: decreases - REM levels: 1. Acetylcholine - Brain region containing cell bodies: pons, basal forebrain, medial septum - Waking levels: high - Slow wave sleep levels: low - REM levels: high 2. Norepinephrine - Brain region containing cell bodies: lcus coeruleus - Waking levels: high - Slow wave sleep levels: low - REM levels: low 3. Serotonin - Brain region containing cell bodies: raphe nuclei - Waking levels: high - Slow wave sleep levels: decreasing - REM levels: low 4. Histamine - Brain region containing cell bodies: tuberomammillary nucleus - Waking levels: high - Slow wave sleep levels: low - REM levels: low 5. Orexin - Brain region containing cell bodies: lateral hypothalamus - Waking levels: high - Slow wave sleep levels: low - REM levels: low
Disorders of sleep: insomnia
Affect approximately 25% of the population occasionally - 9% regularly Primary insomnia: difficulty falling asleep after going to bed or after awakening during the night Secondary insomnia: an inability to sleep due to another mental or physical condition - pain, substance use, or a psychological or neurological condition Many people spend much of their time in a sleep-deprived state - Chronic sleep deprivation can lead to serious health problems - including increased risk of obesity, diabetes, and cardiovascular disease
Stages of sleep: EEG - desynchronized
Alert and attentive or is thinking actively - Beta wave lengths Cells are active at random Seen as small, chaotic waveforms without a clear pattern in the EEG data Extrastriate cortical arousal related to dreams - Activity in brain areas associated with talking and listening in dreams - Increased cortical and subcortical motor activity associated with movements in dreams
REM sleep behaviour disorder
Behavior of people with this disorder corresponds with the contents of their dreams in REM Appears to be a neurodegenerative disorder with at least some genetic component - Associated with neurodegenerative disorders - Parkinson's disease These disorders are called α-synucleinopathies because they involve the inclusion of α-synuclein protein in degenerating neurons Can be caused by brain damage—in some cases to the neural circuits in the brainstem that control the phenomena of REM sleep Fail to exhibit paralysis during REM sleep Treated by clonazepam, a benzodiazepine
Functions of slow-wave sleep: effects of sleep deprivation - human studies - slow wave sleep function
Brain expends 20% of the body's energy during quiet wakefulness Cerebral metabolic rate and blood flow decline during slow-wave sleep - falling to about 75% of the waking level Regions that have the highest levels of activity during waking show the highest levels of delta waves—and the lowest levels of metabolic activity— during slow-wave sleep - Presence of slow- wave activity in a particular region of the brain appears to indicate that that region is resting When awoken in slow wave sleep - people are groggy leading to believe that the cerebral cortex has been shut down and has not yet resumed its functioning During slow-wave sleep the brain is indeed resting Slow-wave sleep.sleep facilitates learning
Functions of slow-wave sleep: effects of physical activity on slow-wave sleep
Brain may need slow-wave sleep to recover from the day's physical activities The relationship between sleep and exercise does not appear to be very strong - there are no changes in slow-wave or REM sleep of healthy participants who spent six weeks resting in bed - If sleep repairs wear and tear, we would expect these people to sleep less Studying the sleep of individuals with severe paralysis due to spinal cord injury - small decrease in slow-wave sleep as compared with uninjured people Conclusion: sleep provides the body with rest, its primary function appears to be something else.
Brain activity during sleep: brain activity in REM and dreaming - eye movement
Eye movements in REM sleep are related to the visual imagery that occurs while we dream Eye movements are similar to what would have been expected if the participants had actually been watching the events in their dreams 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: narcolepsy - cataplexy - emotional component
Cataplexy is usually precipitated by strong emotional reactions or by sudden physical effort Laughter, anger, or an effort to catch a suddenly thrown object can trigger a cataplectic attack - People who do not have cataplexy sometimes lose muscle strength after a bout of intense laughter Patients with narcolepsy often try to avoid thoughts and situations that are likely to evoke strong emotions because they know that these emotions are likely to trigger cataplectic attacks
Neural control of arousal: orexin - location and projections
Cell bodies of neurons that secrete orexin are located in the lateral hypothalamus (LH) 7,000 orexinergic neurons in the human brain Axons: project to almost every part of the brain - cerebral cortex and all of the regions involved in arousal and wakefulness - the locus coeruleus, raphe nuclei, tuberomammillary nucleus, and acetylcholinergic neurons in the dorsal pons and basal forebrain - Orexin has an excitatory effect in all of these regions. Lateral hypothalamus (LH) --> cerebral cx, arousal system: locus ceruleus (NE), raphe (5HT), tuberomammillary n. (histamine), dorsal pons and basal forebrain (ACh)
Brain activity during sleep: brain activity in REM and dreaming
Cerebral blood flow during REM: 1. High in extrastriate cortex (visual association cortex) 2. Low in the striate (primary) visual cortex 3. Low in the prefrontal cortex The lack of activity in the striate cortex reflects: eyes are not receiving visual input High level of activity in the extrastriate cortex: visual hallucinations that occur during dreams Prefrontal cortex: dreams are characterized by good visual images but are poorly organized with respect to time
Brain activity during sleep: brain activity in slow wave sleep
Changes in brain activity accompany dreamlike imagery experienced during slow-wave sleep Regional cerebral blood flow is generally decreased throughout the brain - Increases: visual and auditory cortexes - the neural basis for the dreamlike imagery experienced during slow-wave sleep - Decreased: thalamus and cerebellum
Neural control of arousal: histamine - studies
Control of wakefulness is shared with the other neurotransmitters discussed in this section - Experiment: found that mice with a targeted mutation that blocks the synthesis of histamine showed normal amounts of spontaneous wakefulness. The animals showed less arousal in response to environmental stimuli Normal mice placed in a novel environment remain awake for 2-3 hours. Histamine-deprived mice fell asleep within a few minutes
Neural control of sleep/wake transitions: circadian factors
Daily behavior and physiological rhythms Internal clocks Zeitgebers: light stimulus that resets the biological clock responsible for circadian rhythms
Biological clocks: circadian rhythms
Daily rhythms in behavior and physiological processes are found throughout the plant and animal world A circadian rhythm is one with a cycle of approximately 24 hours Some of these rhythms are passive responses to changes in illumination. A free-running clock, with a cycle of approximately 25 hours, controls some biological functions - sleep and wakefulness - Regular daily variation in the level of illumination normally keeps the clock adjusted to 24 hours. Rhythms are controlled by mechanisms within the organism—by "internal clocks The animal must possess an internal, biological clock - Rat's clock was not set precisely to 24 hours - When the illumination was held constant, the clock ran a bit slow - The animal began its bout of activity approximately 1 hour later each day
Neural control of transitions to REM: flip-flop circuits impairment in narcolepsy
Daytime sleepiness/fragmented sleep in narcolepsy: without the influence of orexin, the sleep/waking flip-flop becomes unstable - The release of orexin in the REM-OFF region normally keeps the REM flip-flop in the off state - With the loss of orexinergic neurons, emotional episodes (laughter or anger) which activate the amygdala, tip the REM flip-flop into the ON state --> attack of cataplexy Study: When people with cataplexy watched humorous sequences of photographs, the hypothalamus was activated less, and the amygdala was activated more - Loss of orexinergic neurons removed an inhibitory influence of the hypothalamus on the amygdala. The increased amygdala activity could partially account for the increased activity of REM-ON neurons that occurs even during waking in people with cataplexy
Disorders of sleep: narcolepsy - physiological basis - treatment
Drugs Sleep attacks: diminished by stimulants - methylphenidate (Ritalin), a catecholamine agonist The REM sleep phenomena (cataplexy, sleep paralysis, and hypnagogic hallucinations): alleviated by antidepressant drugs - facilitate both serotonergic and noradrenergic activity
Sleep and learning: declarative memories
Explicit memories Include those that people can talk about - memories of past episodes in their lives Memories of the relationships between stimuli or events - spatial relationships between landmarks that permit us to navigate around our environment Semantic: facts, what? - Paired associates tasks - Mental tasks - Visiting a museum Episodic: events, when, where - Hippocampus and virtual reality route learning - Thoughts related to virtual reality navigation task - Motor learning task versus immobilized arm
Stages of sleep: stage 2
EEG during this stage is generally irregular but contains periods of theta activity, sleep spindles, and K complexes The person is sleeping soundly now If awakened, she might report that she has not been asleep 15 minutes later - enters slow-wave sleep
Stages of sleep: wakefulness
EEG: alpha activity and beta activity
Problems associated with slow-wave sleep: sleep-related eating disorder
Eating during the night while they were asleep Almost half became overweight When you realise what you are doing: strategies to keep them from eating - keeping their food under lock and key, setting alarms Heredity may play a role Treatment: dopaminergic agonists or topiramate, an antiseizure medication, and may be provoked by zolpidem, a benzodiazepine agonist that has been used to treat insomnia
Stages of sleep: measurements of sleep - electrooculogram (EOG)
Electrical potential from eyes, recorded by means of electrodes placed on skin around them; detects eye movements
Stages of sleep: measurements of sleep - electromyogram (EMG)
Electrical potential recorded from electrode placed on or in muscle. Placed on the face to monitor muscle activity during sleep
Stages of sleep: measurements of sleep - electroencephalogram (EEG)
Electrodes to the scalp to monitor the brain's activity Records many neurons all at once, reporting the sum of their electrical activity Synchronized Desynchronized
Neural control of arousal: acetylcholine (ACh) - during REM and slow-wave sleep
Experiment - Investigators measure acetylcholine release in the hippocampus and neocortex - two regions whose activity is closely related to an animal's alertness and behavioral arousal - Results: levels of ACh in these regions were high during waking and REM sleep (EEG displayed desynchronized activity). Low during slow-wave sleep
Neural control of sleep/wake transitions: arousal neurons - stability in flip-flop circuits
Flip-flop advantage: switches from one state to another quickly Greatest advantage is being either asleep or awake - a state that characteristics of both would be maladaptive. Problem with flip-flops: can be unstable Example of instability: Narcolepsy and animals to the orexinergic system of neurons - They have great difficulty remaining awake when nothing interesting is happening. Have trouble remaining asleep for an extended amount of time - Show intrusions of the characteristics of REM sleep at inappropriate times
Stages of sleep: stage 3
High-amplitude delta activity (less than 3.5 Hz) 20 minutes plus 35 minutes in duration Two stages: The differences are just that 3a is the transition - 3a - 20 minutes: transition from theta to delta - 3b - 45 minutes: most of your time in delta Delta activity transitions from less than 20-50% of the time (3a) to more than 50% of the time (3b) Slow wave sleep People are unreactive to all but intense stimuli during slow-wave sleep and, if awakened, act groggy and confused Stage 3 is the deepest stage of sleep Night terrors Dreaming: report she was not dreaming when awoken. If we question them more carefully, they might report the presence of a thought, an image, or some emotion. Consolidation of declarative memories
Biological clocks: circadian rhythms - humans
Humans exhibit circadian rhythms Normal period of inactivity begins several hours after the start of the dark portion of the day/night cycle and persists for a variable amount of time into the light portion Without the benefits of modern civilization we would probably go to sleep earlier and get up earlier than we do - Using artificial lights to delay our bedtime and window shades to extend our time for sleep Under constant illumination our biological clocks will run free, gaining or losing time like a watch that runs too slow or too fast Different people have different cycle lengths - most people will begin to live a "day" that is approximately 25 hours long because of our advances
Stages of sleep: EEG - synchronized
If the cells are active at about the same time Large, clear wave in the EEG data Sleep and quiet awake Delta, theta and alpha wavelengths
Sleep and learning: nondeclarative memories
Implicit memories Include those gained through experience and practice that do not necessarily involve an attempt to "memorize" information - learning to drive a car, throwing and catching a ball, or recognizing a person's face. Habituation Conditioning Classical Conditioning Operant Conditioning - Nondeclarative visual discrimination task Spatial Learning (nonverbal animals) Priming Perceptual Learning - Mirror tracing task Procedural learning/skills
Neural control of sleep/wake transitions: arousal neurons - stability in flip-flop circuits - orexinergic neurons
Important function of orexinergic neurons: help stabilize the sleep/waking flip-flop through their excitatory connections to the wakefulness neurons Activity of this system of neurons tips the activity of the flip-flop toward the waking state - promoting wakefulness and inhibiting sleep Staying awake when bored depends on maintaining a high rate of firing of your orexinergic neurons - keeping the flip-flop in the waking state Study: mice with a targeted mutation against the orexin gene showed normal amounts of sleep and waking, but their bouts of wakefulness and slow-wave sleep were very brief - many more transitions between sleep and waking - Conclusion: orexinergic neurons help stabilize the sleep/waking flip-flip
Neural control of arousal: acetylcholine (ACh) - overview of the three neurons
Important neurotransmitter involved in arousal - especially the cerebral cortex Two groups of acetylcholinergic neurons: 1) pons and 2) basal forebrain - When stimulated: activation and cortical desynchrony Third group of acetylcholinergic neurons: medial septum - Controls the activity of the hippocampus.
Neural control of arousal: serotonin
Involved in activating behavior Almost all of the brain's serotonergic neurons are found in the raphe nuclei - located in the medullary and pontine regions of the reticular formation Axons: project to many parts of the brain - thalamus, hypothalamus, basal ganglia, hippocampus, and neocortex
Neural control of arousal: histamine
Involved in the control of wakefulness and arousal The cell bodies of histaminergic neurons are located in the tuberomammillary body (TMB) of the hypothalamus Axons: project to the cerebral cortex, thalamus, basal ganglia, basal forebrain, and other regions of the hypothalamus - Projections to the cerebral cortex: directly increase cortical activation and arousal - Projections to the basal forebrain and dorsal pons: indirectly increase cortical activation and arousal by increasing the release of acetylcholine in the cerebral cortex Antihistamines - are used to treat allergies, can cause drowsiness - They do so by blocking histamine H2 receptors in the brain - More modern antihistamines cannot cross the blood-brain barrier, so they do not cause drowsiness.
Stages of sleep: wavelengths - beta activity
Irregular Mostly low-amplitude waves of 13-30 Hz. Desynchrony
Functions of slow-wave sleep: effects of sleep deprivation - animal studies
Kept rats from sleeping without forcing them to exercise continuously A group of control animals exercised just as much as the experimental participants but were able to engage in normal amounts of sleep Sleep deprivation had serious effects - Control animals: remained healthy - Experimental animals: looked sick and stopped grooming their fur, became weak and uncoordinated and lost their ability to regulate their body temperature. They began eating more food than normal - their metabolic rates became so high that they continued to lose weight. They died Cause of death is not understood - The rats' brains appeared to be normal, and there were no obvious signs of inflammation or damage to other internal organs - Levels of stress hormones were not unusually high - the deaths could not be attributed to simple stress If they were given a high-calorie diet to compensate for their increased metabolic rate, the rats lived longer, but eventually they succumbed Damage to parts of the basal forebrain causes insomnia, and if the animals do not recover from their sleeplessness, they die
Disorders of sleep: narcolepsy - physiological basis - orexinergic neurons
Loss of orexinergic neurons is the cause of most cases of narcolepsy in humans Study: complete absence of orexin in seven of the nine patients with narcolepsy - Cause of narcolepsy in seven patients: hereditary disorder that caused the immune system to attack and destroy orexin-secreting neurons - The narcolepsy seen in the two patients with high levels of orexin may have been caused by a mutation of a gene responsible for production of the orexin-B receptor—the same mutation that causes canine narcolepsy. Most patients with narcolepsy are born with orexinergic neurons. During adolescence - the immune system attacks these neurons, and the symptoms of narcolepsy begin Another explanation: mutation of the gene responsible for the production of orexin
Brain activity during sleep: brain activity in REM and dreaming - lucid dreaming
Lucid dreaming: an awareness they are dreaming and not awake. Activation of the prefrontal cortex could be involved - May also occur in non-REM sleep. Study of the prefrontal cortex activity in lucid dreaming - Three nights in a sleep research lab - Night one: acclimated to the lab - Night two: transcranial direct current stimulation (tDCS) was used to apply a weak current to the scalp of participants to activate the dorsolateral prefrontal cortex - Night three: participants received a sham activation - Participants were awakened after each REM episode and asked to report their dreams. Participants reported more lucid dreams in response to tDCS versus sham stimulation - Conclusion: hints at the role of at least one brain region involved in REM lucid dreaming
Neural control of sleep/wake transitions: arousal neurons - preoptic area - ventrolateral preoptic area (vIPOA)
Majority of the sleep neurons are located in the ventrolateral preoptic area (vlPOA). Activity of these neurons increases during sleep Damage to vlPOA neurons: suppresses sleep
Problems associated with slow-wave sleep
Maladaptive behaviors: bedwetting, sleepwalking (somnambulism), and night terrors - These occur most frequently in children Bedwetting: cured by training methods - having a special electronic circuit ring a bell when the first few drops of urine are detected in the bed sheet Night terrors: anguished screams, trembling, a rapid pulse, and usually no memory of what caused the terror - Night terrors and somnambulism usually cure themselves as the child gets older - Neither of these phenomena is related to REM sleep A sleepwalking person is not acting out a dream - Sleepwalking may have a genetic component - especially when it occurs in adulthood - People can engage in complex behaviors while sleepwalking
Disorders of sleep: narcolepsy - physiological basis - treatment - modafinil
Modafinil: stimulant drug whose precise site of action is still unknown, is widely used to treat narcolepsy Administration of modafinil increased the expression of Fos protein in orexinergic neurons - the neurons had been activated The drug must act on other targets, because the drug treats the symptoms of people with narcolepsy, whose brains lack these neurons.
Neural control of arousal: serotonin - rate during different stages
Most active during waking Slow wave sleep: firing rate declines REM sleep: close to zero - Once the period of REM sleep ends, the neurons temporarily become very active
Neural control of arousal: norepinephrine - neurons in the locus coeruleus
Neurons of the locus coeruleus (dorsal pons) give rise to axons that branch widely, releasing norepinephrine throughout the neocortex, hippocampus, thalamus, cerebellar cortex, pons, and medulla - They potentially affect widespread and important regions of the brain Sprinkler system of the brain Activity of noradrenergic LC neurons increases an animal's vigilance
Seasonal affective disorder
Normally, melatonin secretion begins in the evening, approximately six hours before the midpoint of sleep Most people with seasonal affective disorder begin secreting melatonin earlier, showing a phase delay between cycles of melatonin and sleep A few people with this disorder show a phase advance, with melatonin secretion beginning at a later time
Neural control of sleep: adenosine
Nucleoside neuromodulator Astrocytes: maintain a small stock of nutrients in the form of glycogen Increased brain activity: glycogen is converted into fuel for neurons - Prolonged wakefulness --> decrease in glycogen in the brain Decrease of glycogen --> an increase in the level of extracellular adenosine, which has an inhibitory effect on neural activity. This accumulation of adenosine serves as a sleep-promoting substance. Adenosine accumulates during wakefulness and is reduced during slow-wave sleep - During slow-wave sleep: neurons in the brain rest. Astrocytes renew their stock of glycogen - Prolonged wakefulness: more adenosine accumulates - inhibits neural activity and produces the cognitive and emotional effects that are seen during sleep deprivation Caffeine blocks the adenosine receptors, preventing the inhibitory effect on neural activity and reducing the effects of sleep deprivation. Study: - Investigator prepared a targeted mutation in the brains of mice that interfered with the release of adenosine by astrocytes - Results: animals spent less time than normal in slow-wave sleep
Functions of slow-wave sleep: effects of sleep deprivation - human studies - sleeping after deprivation
Once sleep deprived - most of people sleep longer the next night or two, but they never regain all of the sleep they lost Case a 17-year-old boy stayed awake for 264 hours - Boy slept for a little less than 15 hours and awoke feeling fine - He slept slightly more than 10 hours the second night and just under 9 hours the third - Almost 67 hours of missing sleep were never made up Percentages of recovery were not equal for all stages of sleep - Only 7% of stages 1 and 2 were made up - 68% of slow-wave sleep and 53% of REM sleep were made up Slow-wave sleep and REM sleep are more important than the other stages
Stages of sleep: overview of the night - cycles
Once you enter REM sleep the first time - the rest of the night sleep alternates between periods of REM and non-REM sleep Each cycle is approximately 90 minutes long, containing a 20- to 30-minute bout of REM sleep - An 8-hour sleep will contain four or five periods of REM sleep REM sleep and stage 1 sleep are placed on the same line because similar patterns of EEG activity occur at these times Most slow-wave sleep occurs during the first half of night - Subsequent bouts of non-REM sleep contain more and more stage 2 sleep, and bouts of REM sleep become more prolonged
Neural control of sleep: enzyme adenosine deaminase
People differ in their sleep need Genetic factors affect the typical duration of a person's slow-wave sleep. Variability in the gene that encodes for an enzyme, adenosine deaminase, which is involved in the breakdown of adenosine can influence the amount of sleep someone needs - People with the G/A allele for this gene (encodes for a form of the enzyme that breaks down adenosine more slowly) spent approximately 30 minutes more time in slow-wave sleep than did people with the more common G/G allele - Levels of adenosine in people with the G/A allele decreased more slowly during slow-wave sleep and the slow-wave sleep of these people was prolonged
Neural control of arousal: orexin
Peptide neurotransmitter Called hypocretin and orexin by others Exploring, eating, metabolism (motivation) Orexin plays a crucial role in the physiological and behavioral effects of some drugs High rate of firing: alert or active waking - The highest rate of firing was seen when the rats were engaged in exploratory activity Low rate of firing: quiet waking, slow-wave sleep, and REM sleep
Disorders of sleep: insomnia - treatment
Pharmacological and nonpharmacological interventions can be effective Nonpharmacological interventions: cognitive behavior therapy (CBT), progressive relaxation techniques, and changes in sleep hygiene Sleep hygiene recommendations: maintaining a consistent sleep schedule and keeping bedrooms dark, quiet, and cool Pharmacological interventions: a class of drugs called the hypnotics. - Zolpidem (Ambien) and zaleplon (Sonata) which are agonists at the GABAA receptor Benzodiazepines and over-the-counter antihistamines (diphenhydramine) are also used to treat insomnia - These drugs can produce side effects: sleepiness or difficulty concentrating the following day Chronic use of sleep-promoting drugs can lead to tolerance and rebound insomnia (a return and increase in insomnia) when their use is ended
Brain activity during sleep: brain activity in REM and dreaming - overview
Prefrontal cortex: Low activity during REM; shows lack of organization and planning in dreams. Extrastriate cortex: High activity during REM; reflects visual hallucinations during dreaming. Striate cortex: Low activity during REM due to lack of visual input
Neural control of sleep/wake transitions: arousal neurons - preoptic area
Preoptic area/sleep neurons: most involved in control of sleep - Contains neurons whose axons form inhibitory synaptic connections with the brain's arousal neurons When active: suppress the activity of our arousal neurons, and we fall asleep Study: destruction of the preoptic area produced total insomnia in rats. - The animals fell into a coma and died - Average survival time was three days Electrical stimulation of the preoptic area: causes drowsiness and sleep Sleep neurons secrete the inhibitory neurotransmitter GABA and they send their axons to the five brain regions involved in arousal - Inhibition of these regions: necessary condition for sleep
Disorders of sleep: narcolepsy - sleep attacks
Primary symptom A sleep attack: an overwhelming urge to sleep that can happen at any time. Occurs most often under monotonous, boring conditions Sleep (which appears to be entirely normal) generally lasts for 2-5 minutes The person usually wakes up feeling refreshed
Disorders of sleep: insomnia - diagnosing problems
Problem in identifying insomnia: unreliability of self-reports - Most patients they tell their physician that they sleep very little at night, and the drug is prescribed on the basis of this testimony. - Very few patients are observed during a night's sleep in a sleep laboratory --> insomnia is one of the few medical problems that physicians treat without having direct clinical evidence for its existence. People who complain of insomnia: most of them underestimate their sleep time - Study: talked to people in a sleep laboratory who complained of insomnia and people who did not. They found no differences between the two groups in time spent sleeping. They did find personality differences, which could account for the complaints
Functions of REM sleep
REM sleep is a time of intense physiological activity - eyes movement, heart rate and breathing irregularities, brain becomes more active REM sleep deprivation: - As deprivation progressed, participants had to be awakened from REM sleep more frequently - the "pressure" to enter REM sleep built up. - After several days of REM sleep deprivation, participants would show a rebound phenomenon when permitted to sleep normally Rebound phenomenon: they spent a much greater-than-normal percentage of the recovery night in REM sleep - Suggests that there is a need for a certain amount of REM sleep - REM sleep is controlled by a regulatory mechanism - If selective deprivation causes a deficiency in REM sleep, the deficiency is made up later, when uninterrupted sleep is permitted. The highest proportion of REM sleep is seen during the most active phase of brain development - REM sleep plays a role in this process Species in which young are born with immature brains spend much more time in REM sleep than species with young born with well-developed brains REM sleep facilitates the massive changes in the brain that occur during development but also some of the more modest changes responsible for learning that occur throughout the lifespan REM sleep facilitates learning
Sleep and learning: overview
REM sleep: - Consolidation of nondeclarative memories Slow-wave sleep - Consolidation of declarative memories - If you think about a task when you are sleeping - greater performance - Sleeping brain rehearses information that was acquired during the previous period of wakefulness
Stages of sleep: overview of the cycles - principle characteristics of REM and slow-wave sleep
REM sleep: 1. EEG desynchrony (rapid, irregular waves) 2. Lack of muscle tone 3. Rapid eye movement 4. Penile erection or vaginal secretion 5. Dreams Slow-wave sleep 1. EEG synchrony (slow wave) 2. Moderate muslce tonus 3. Slow or absent eye movements 4. Lack of gentile activity 5. Thoughts
Neural control of transitions to REM: flip-flop circuits for transitions to REM
Rate of cerebral metabolism is equal during REM and waking If the skeletal muscles of the body were not paralyzed, the level of physical activity would also be high REM sleep is controlled by a flip-flop similar to the one that controls cycles of sleep and waking REM flip-flop controls our cycles of REM sleep and slow-wave sleep.
Stages of sleep: wavelengths - alpha activity
Regular, medium-frequency waves of 8-12 Hz The brain produces this activity when a person is resting quietly, not particularly aroused or excited and not engaged in strenuous mental activity Sometimes occur when a person's eyes are open, they are much more prevalent when they are closed
Neural control of sleep/wake transitions: homeostatic
Regulation of optimal body conditions (internal milieu) Presence or absence of adenosine
Disorders of sleep: narcolepsy - physiological basis
Relatively rare 1 in 2,000 people Gene found on chromosome 6 Strongly influenced by unknown environmental factors Study of dogs: found a mutation of a specific gene responsible for canine narcolepsy - The product of this gene is a receptor for orexin - There are two orexin receptors, A and B - the mutation responsible for canine narcolepsy involves the orexin-B receptor Destruction of the orexin system produced the symptoms of narcolepsy
Neural control of sleep/wake transitions: allostatic
Responding to stress to restore balance Hormonal and neural responses to stress Neuropeptides (e.g. orexin) involved in hunger & thirst
Functions of slow-wave sleep: effects of sleep deprivation - human studies - slow wave sleep function - fatal familia insomnia
Results in damage to portions of the thalamus Symptoms: deficits in attention and memory, followed by a dreamlike, confused state; loss of control of the autonomic nervous system and the endocrine system; increased body temperature; and insomnia The first signs of sleep disturbances: reductions in sleep spindles and K complexes As the disease progresses: slow-wave sleep completely disappears, and only brief episodes of REM sleep (without the accompanying paralysis) remain The disease is fatal Man diagonised who had other family members die from it: - Had a form of that usually causes death within 12 months - He enlisted the aid of several physicians to administer drugs and treatments designed to help him sleep - For several months the treatments did help him to sleep, and the man survived about a year longer than would have been expected, with a higher quality of life during the course of his illness Study with five people with fatal familial insomnia: - Symptoms: insomnia, memory loss, and autonomic dysfunction and prominent weight loss.
Stages of sleep: stage 2 - sleep spindles
Short bursts of waves of 12-14 Hz 1-5 spindles per minute originate in reticular thalamic nucleus Burst of activity, frequently more common than the K complexes Under certain drugs - you may lack sleep spindles or K complexes Increased numbers of sleep spindles - increased scores on tests of intelligence Consolidation of memories - Consolidation information you have gotten throughout the day - Facilitate making short term long term memory
Sleep and learning
Sleep aids in the consolidation of long-term memories Slow-wave sleep and REM sleep play different roles in memory consolidation There are two major categories of long-term memory: declarative memory and nondeclarative memory - Slow-wave sleep and REM sleep play different roles in the consolidation of declarative and nondeclarative memories.
What is sleep?
Sleep is a behavior - Characterizes sleep: the insistent urge of sleepiness (a motivation) forces us to seek out a quiet, warm, comfortable place; lie down; and remain there fore several hours (a behavior) Best research on human sleep is conducted in sleep labratories
Functions of slow-wave sleep
Sleep is a universal phenomenon among vertebrates Sleep appears to be essential to survival
Functions of slow-wave sleep: dolphins
Sleep is found in some species of mammals that would seem to be better off without it - Some species of marine mammals have developed an extraordinary pattern of sleep: The cerebral hemispheres take turns sleeping, presumably because that strategy always permits at least one hemisphere to be alert and keep the animal from drowning - The eye contralateral to the active hemisphere remains open The bottlenose dolphin (Tursiops truncatus) and the porpoise (Phocoena phocoena) both sleep with one hemisphere at a time - Slow-wave sleep occurs independently in the left and right hemispheres.
Neural control of arousal
Sleep is not a unitary condition but consists of several different stages with very different characteristics Waking state is nonuniform Sleepiness has an effect on wakefulness - Even when we are not sleepy, our alertness can vary Neurotransmitters that play a role in alertness and wakefulness: 1. Acetylcholine 2. Norepinephrine 3. Serotonin 4. Histamine 5. Orexin
Functions of slow-wave sleep: effects of sleep deprivation - human studies
Sleep is not needed to keep the body functioning normally Sleep deprivation does not interfere with people's ability to perform physical exercise No evidence of a physiological stress response to sleep deprivation. Primary role of sleep does not seem to be rest and recuperation of the body People's cognitive abilities are affected - perceptual distortions or even hallucinations and have trouble concentrating on mental task One night of sleep deprivation: ability to recognize emotional facial expressions is impaired Sleep provides the opportunity for the brain to rest
Neural control of sleep: monitoring the amount of sleep we need
Sleep is regulated - an organism deprived of slow-wave sleep or REM sleep will make up at least part of the missed sleep when permitted to do so Amount of slow-wave sleep a person obtains during a daytime nap is deducted from the amount of slow-wave sleep he or she obtains the next night Some physiological mechanism monitors the amount of sleep that an organism needs
Disorders of sleep: narcolepsy - sleep paralysis
Sleep paralysis: an inability to move just before the onset of sleep or on waking in the morning A person can be snapped out of sleep paralysis by being touched or by hearing someone call his or her name The mental components of REM sleep intrude into sleep paralysis - the person dreams while lying awake, paralyzed Hypnagogic hallucinations: dreaming while lying awake - often alarming or even terrifying
Why do we sleep?
Sleepiness is one of the most insistent drives we experience The primary function of slow-wave sleep is to permit the brain to rest REM sleep promotes brain development Slow-wave sleep and REM sleep promote different types of learning
Neural control of arousal: serotonin - function
Stimulation of the raphe nuclei causes locomotion and cortical arousal Serotonin neurons facilitate continuous, automatic movements - pacing, chewing, and grooming - Serotonergic neurons: decrease when animals engage in orienting responses to novel stimuli Facilitate ongoing activities Suppress the processing of sensory information, preventing reactions that might disrupt the ongoing activities
Sleep and learning: study on nondeclarative tasks
Study 1: looked at the effects of a nap on memory consolidation. Participants learn a nondeclarative visual discrimination task at 9:00 a.m. Participants' ability to perform the task was tested 10 hours later Some of the participants took a 90-minute nap during the day between training and testing - Investigators recorded the EEGs of the sleeping participants to determine which of them engaged in REM sleep and which of them did not. (All of them engaged in slow-wave sleep, because this stage of sleep always comes first in healthy people.) Results: - Did not nap: did worse when they were tested at 7:00 p.m. than it had been at the end of training - Did nap (slow-wave sleep): did about the same during testing as they had done at the end of training - Did nap (REM sleep): performed significantly better. Conclusion: REM sleep strongly facilitated the consolidation of a nondeclarative memory
Sleep and learning: study on nondeclarative and declarative tasks
Study 2: trained participants on two tasks: a declarative task (learning a list of paired words) and a nondeclarative task (learning paper in a mirror) Some of participants were permitted to take a nap lasting for about 1 hour - were awakened before entering REM sleep Participants' performance on the two tasks were tested 6 hours after the original training Results: - Nap (slow-wave): improved performance on declarative task but had no effect on nondeclarative task Conclusion: REM sleep facilitates consolidation of nondeclarative memories and that slow-wave sleep facilitates consolidation of declarative memories
Sleep and learning: study on learning locations
Study 3: participants learn their way around a computerized virtual-reality town They must learn the relative locations of landmarks and streets that connect them so that they can find particular locations when the experimenter "placed" them at various starting points - Hippocampus plays an essential role in learning of this kind Used functional brain imaging to measure regional brain activity - the same regions of the hippocampus were activated during route learning and during slow-wave sleep the following night. These patterns were not seen during REM sleep
Neural control of arousal: acetylcholine (ACh) - neurons in the basal forebrain
Study: electrically stimulated a region of the dorsal pons - Results: the stimulation activated the cerebral cortex and increased the release of ACh in the dorsal pons by 350% - Conclusion: A group of acetylcholinergic neurons located in the basal forebrain forms an essential part of the pathway that is responsible for the increase of ACh If the neurons in the basal forebrain were deactivated --> the activating effects of the pons stimulation were abolished Drugs that activate the neurons in the basal forebrain --> wakefulness Neurons in the basal forebrain: high rate of firing during waking and REM sleep Neurons in the basal forebrain: low rate of firing during slow-wave sleep
Neural control of arousal: norepinephrine - studies
Study: recorded the activity of noradrenergic neurons of the LC across the sleep/wake cycle in unrestrained rats - Results: this activity was closely related to behavioral arousal: The firing rate of these neurons was high during wakefulness, low during slow- wave sleep, and almost zero during REM sleep. Within a few seconds of awakening, the rate of firing increased dramatically Study: used a viral vector to insert genes for two photosensitive proteins, ChR2 and NpHR, into noradrenergic cells of the locus coeruleus - Exposure of ChR2 to blue light activates the neurons - Exposure of NpHR to yellow light inhibits the neurons - Results: stimulation of the neurons caused immediate waking, and that inhibition decreased wakefulness and increased slow-wave sleep. Study: recorded the electrical activity of noradrenergic LC neurons in monkeys performing a task that required them to watch for a particular stimulus that would appear on a video display - Resutls: monkeys performed best when the rate of firing of the LC neurons was high. After the monkeys worked for a long time at the task, the neurons' rate of firing decreased, and so did the monkeys' performance - Conclusion: activation of LC neurons (and their release of norepinephrine) increases vigilance
Neural control of arousal: orexin - study
Study: used genetic transfer to insert ChR2 protein into orexinergic neurons of the lateral hypothalamus of mice Results: optogenetic activation of these neurons with blue light awakened the animals from either REM or non-REM sleep
Neural control of transitions to REM: REM-ON
Sublaterodorsal nucleus (SLD) REM-ON neurons: cells that fire at a high rate only during REM Stimulation of the REM-ON region with infusions of glutamate agonists: elicits most elements of REM sleep. Inhibition of this region with GABA agonists disrupts REM sleep
Neural control of sleep: explanation for the motoring system - substance production
Substances do not appear to be found in the general circulation of the body If sleep is controlled by chemicals, these chemicals are produced within the brain and act there - Evidence: each hemisphere of the brain incurs its own sleep debt. Researchers deprived a bottlenose dolphin of sleep in only one hemisphere. When they allowed the animal to sleep normally, they saw a rebound of slow-wave sleep only in the deprived hemisphere
Stages of sleep: stage 2 - K complexes
Sudden, sharp waveforms Usually found only in stage 2 sleep Spontaneously occur at about 1 per minute but can be triggered by noises—especially unexpected noises. Tries to inhibit your reaction to large noises - facilitate you going to sleep Consisted of isolated periods of neural inhibition Appear to be the forerunner of delta waves, which appear in the deepest levels of sleep
Functions of slow-wave sleep: effects of cognitive activity on slow-wave sleep
Tasks that demand alertness and mental activity increase glucose metabolism in the brain - Most significant increases are seen in the frontal lobes, where slow-wave activity is most intense during non-REM sleep Experiment - People performed a motor learning task just before going to sleep: hand movements whose directions were indicated by a visual display. - During sleep the participants showed increased slow-wave activity in the region of the neocortex that became active while they were performing the task - Increased activity of these cortical neurons called for more rest during the following night's sleep Follow up study: - Immobilizing one arm for 12 hours produced the opposite result: During sleep the people showed less slow-wave activity in the regions of the neocortex that received somatosensory information from that arm and controlled its movements Experiment 3: - Experimenters found a way to increase mental activity without affecting physical activity and without causing stress - Participants thought they were going to do reading tasks but were taken out for the day. They did fun activities and watched a movie. They were driven and did not become overheated or tired by physical exercise - After the movie, they returned to the sleep laboratory - They said they were tired, and they readily fell asleep - Sleep duration was normal, and they awoke feeling refreshed - Their slow-wave sleep was increased After mental exercise, the brain appears to have needed more rest than usual
Neural control of transitions to REM: REM-ON and REM-OFF
The REM-ON and REM-OFF regions are interconnected by means of inhibitory GABAergic neurons The mutual inhibition of the ON and OFF systems means that they function like a flip-flop: only one region can be active at any given time
Neural control of sleep: simple explanation for the motoring system
The body produces a sleep-promoting substance that accumulates during wakefulness and is destroyed during sleep - The longer someone is awake, the longer he or she has to sleep to deactivate this substance REM sleep deprivation produces an independent REM sleep debt -therefore there might have to be two substances: one for each stage of sleep
Functions of slow-wave sleep: effects of sleep deprivation - human studies - slow wave sleep function - free radicals and rest time
The brain needs rest to recover from its waking activity Free radicals: waste products produced by the high metabolic rate associated with waking activity. They are chemicals that contain at least one unpaired electron - They are highly reactive oxidizing agents Oxidative stress: free radicals can bind with electrons from other molecules and damage the cells in which they are found Prolonged sleep deprivation causes an increase in free radicals and resulted in oxidative stress Slow-wave sleep: the lowered rate of metabolism permits restorative mechanisms in the cells to destroy the free radicals and prevent their damaging effects
Neural control of arousal: orexin - narcolepsy
The cause of narcolepsy: degeneration of orexinergic neurons in humans and a hereditary absence of one type of orexin receptors in dogs Treatment: modafinil - drug that suppresses the drowsiness associated with this disorder - Alerting effects of modafinil are exerted by stimulating the release of orexin in the TMN - activates the histaminergic neurons located there
Neural control of sleep/wake transitions: arousal neurons - flip-flop circuits for sleep/wake transitions - the sleep/waking flip-flop - figure 9.17
The major sleep-promoting region (vlPOA) and the major wakefulness promoting regions (basal forebrain, pontine regions) are reciprocally connected by inhibitory GABAergic neurons (a) When the flip-flop is in the "wake" state, the arousal systems are active and the vlPOA is inhibited, and the animal is awake (b) When the flip-flop is in the "sleep" state, the vlPOA is active and the arousal systems are inhibited, and the animal is asleep
Neural control of sleep/wake transitions: arousal neurons - flip-flop circuits for sleep/wake transitions
The sleep neurons in the preoptic area receive inhibitory inputs from some of the same regions they inhibit - tuberomammillary nucleus, raphe nuclei, and locus coeruleus - They are inhibited by histamine, serotonin, and norepinephrine Reciprocal inhibition also characterizes an electronic circuit known as a flip-flop - Mutual inhibition provides the basis for establishing periods of sleep and waking A flip-flop can assume one of two states, usually referred to as on or off—or 0 or 1 in computer applications. Either the sleep neurons are active and inhibit the wakefulness neurons, or the wakefulness neurons are active and inhibit the sleep neurons. The sleep/waking flip-flop determines when we wake and when we sleep Because these regions are mutually inhibitory, it is impossible for neurons in both sets of regions to be active at the same time - Sleep neurons in the vlPOA are silent until an animal shows a transition from waking to sleep
Neural control of transitions to REM: REM-OFF
The ventrolateral periaqueductal gray matter (vlPAG): a region of the dorsal midbrain. Contains REM-OFF neurons REM-OFF neuron: suppresses REM sleep Damage to the REM-OFF region/infusions of GABA agonists: dramatically increases REM sleep
Stages of sleep: stage 1
Theta activity The firing of neurons in the neocortex is becoming more synchronized. This stage is a transition between sleep and wakefulness Eyelids: they can slowly open and close, roll upward and downward. About 10 minutes later she enters stage 2 sleep.
Sleep and learning: rehearsing learned information and thinking about tasks
Using a similar virtual reality navigation task as study 3 - investigators awakened participants from slow-wave sleep during an afternoon nap that followed training and asked them to report everything that they were thinking about Results: - Participants whose thoughts were related to the task performed much better during a subsequent session on the navigation task than those who did not report such thoughts Conclusion: although people who are awakened during slow-wave sleep seldom report narrative dreams, the sleeping brain rehearses information that was acquired during the previous period of wakefulness
Neural control of arousal: histamine - function
Wakefulness, arousal to environmental stimuli - Histaminergic neurons did not respond to environmental stimuli unless the stimuli elicited a state of overt attention Activity of histaminergic neurons: high during waking. Low during slow-wave sleep and REM sleep Prevention of the synthesis of histamine/block histamine H1 receptors --> decrease waking and increase sleep Infusion of histamine into the basal forebrain region: increase in waking and a decrease in non-REM sleep The brain's arousal systems promote wakefulness at different times or in different situations and no one of these systems plays a critical role under all conditions
Neural control of sleep/wake transitions: role of orexin in sleep/wake transitions
Waking part of the day/night cycle: orexinergic neurons receive an excitatory signal from the biological clock that controls rhythms of sleep and waking Orexinergic neurons receive signals from brain mechanisms that monitor the animal's nutritional state - Activation from hunger-related signals - Inhibition from satiety-related signals Orexinergic neurons maintain arousal during the times when an animal should search for food - Study: when normal mice are given less food than they would normally eat, they stay awake longer each day Orexinergic neurons receive inhibitory input from the vlPOA - sleep signals that arise from the accumulation of adenosine can eventually overcome excitatory input to orexinergic neurons, and sleep can occur Orexinergic neurons are involved in all three factors that control sleep and wakefulness: homeostatic, allostatic, and circadian.
Neural control of transitions to REM: flip-flop circuits for transitions to REM - REM-ON and REM-OFF region - process
Waking: REM-OFF region receives excitatory input from the orexinergic neurons (LH). This activation tips the REM flip-flop into the off state - Additional excitatory input comes from two sets of wakefulness neurons: 1) the noradrenergic neurons (locus coeruleus) and 2) the serotonergic neurons (raphe nuclei) Switches to sleep phase: slow-wave sleep begins - Activity of the excitatory orexinergic, noradrenergic, and serotonergic inputs to the REM-OFF region begins to decrease - Eventually, REM sleep flip-flop switches to the on state, and REM sleep begins. Once sleep begins: activity of orexinergic neurons ceases - removes one source of the excitatory input to the REM-OFF region As sleep progresses: activity of noradrenergic and serotonergic neurons gradually decreases - more of the excitatory input to the REM-OFF region is removed. The REM flip-flop tips to the on state, and REM sleep begins
Brain activity during sleep
We are not unconsciousness when we are sleep In the morning: usually forget what we experienced while asleep The brain is very active in sleep
Neural control of sleep/wake transitions: flip-flop circuits for sleep/wake transitions overview
flip-flop — one state or another, but not both - 1 or 0 / yes or no / true or false / on or off Flip-flop impairment in narcolepsy Flip-flop circuits control REM muscle paralysis Flip-flop circuits in cortical arousal, rapid eye movements, and genital activity in REM