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Sleep
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Why Do We Need Sleep? Adaptive Evolutionary Function
safety energy conservation/ efficiency Restorative Function body rejuvenation & growth Brain Plasticity enhances synaptic connections memory consolidation
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The ascending arousal system promotes wake
B. A. (A) In the 1970s and 1980s, the neurochemistry of several brainstem ‘arousal’ centers was elaborated. In the contemporary view, the ascending arousal system consist of noradrenergic neurons of the ventrolateral medulla and locus coeruleus (LC), cholinergic neurons (ACh) in the pedunculopontine and laterodorsal tegmental (PPT/LDT) nuclei, serotoninergic neurons (5-HT) in the dorsal raphe nucleus (DR), dopaminergic neurons (DA) of the ventral periaqueductal gray matter (vPAG) and histaminergic neurons (His) of the tuberomammillary nucleus (TMN). These systems produce cortical arousal via two pathways: a dorsal route through the thalamus and a ventral route through the hypothalamus and basal forebrain (BF). The latter pathway receives contributions from the orexin and MCH neurons of the lateral hypothalamic area (LH) as well as from GABA-ergic or cholinergic neurons of the BF. Note that all of these ascending pathways traverse the region at the midbrain-diencephalic junction where von Economo observed that lesions caused hypersomnolence. Fuller, PM, Gooley JJ, Saper CB. Neurobiology of the sleep-wake cycle: sleep architecture, circadian regulation, and regulatory feedback. J Biol Rhythms 21(6): (2006) Slide by Patrick Fuller, PhD and Jun Lu, PhD Modified from Fuller et al., J Biol Rhythms, 2006
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Hypocreatin (orexin)
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Sleep/Waking “Flip-Flop”
vlPOA= ventrolateral preoptic area ACh = acetylcholine NE = norepinephrine 5-HT = serotonin
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Narcolepsy VS Insomnia
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Melatonin: Produced by pineal gland, released at night-inhibited during the day (circadian regulation); initiates and maintain sleep; treat symptoms of jet lag and insomnia Melatonin, ramelteon, and agomelatine are all agonists for melatonin 1 (MT1) and melatonin 2 (MT2) receptors [87]. Ramelteon has an affinity for both receptors that is 3–16 times greater than melatonin, and it has a longer half-life. Agomelatine also has a high affinity for melatonin receptors, in addition to acting as an antagonist at serotonin 5-HT2C receptors to decrease anxiety as well as promote sleep. Both MT1 and MT2 play a role in sleep induction; MT1 activation suppresses firing of SCN neurons, and MT2 receptors are involved in entraining circadian rhythms. Melatonin and the SCN impact sleep and wake in several ways. The SCN receives light signals from the retina, which are transmitted to the dorsal medial hypothalamus (DMH). The DMH acts as a relay center for signals to regions involved in sleep and wake maintenance, including inhibitory inputs to the VLPO and excitatory inputs to the LC [14, 95]. Melatonin acts through MT1 receptors to suppress firing of SCN neurons, thereby disinhibiting the sleep-promoting neurons in the VLPO, suppressing excitatory signals to wake-promoting regions, and increasing sleepiness [87].
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Biological Clocks Suprachiasmatic nucleus Pineal gland
A nucleus situated atop the optic chiasm responsible for organizing circadian rhythms. Pineal gland A gland attached to the dorsal tectum; produces melatonin and plays a role in circadian and seasonal rhythms.
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Coffee
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Coffee During waking, brain consume ATP
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Coffee During waking, brain consume ATP adenosine
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Coffee During waking, brain consume ATP adenosine
Adenosine bind to A1 receptor Inhibit acetylcholine neurons
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Coffee During waking, brain consume ATP adenosine
Adenosine bind to A1 receptor Inhibit acetylcholine neurons Caffeine and Theophylline are A1 antagonist
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Sleep stages Awake Stage 1 Stage 2 Stage 3 Stage 4 Slow wave sleep
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Sleep stages Awake Stage 1 Stage 2 Stage 3 Stage 4
Rapid eye movement sleep (REM) Slow wave sleep (NREM)
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EEG waves
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EEG Electrode Placement
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Classifying EEG brain waves
Frequency: the number of oscillations/waves per second, measured in Hertz (Hz) reflects the firing rate of neurons alpha, beta, theta, delta Amplitude: the magnitude of brain waves, measured in millivolts (mV), gives an indication of the wave’s “power”. The number of neurons firing in synchrony & the distance between the neurons and the recording electrode
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Types and Stages of Sleep: NREM
Stage 1 – eyes are closed and relaxation begins; the EEG shows alpha waves; one can be easily aroused Stage 2 – EEG pattern is irregular with sleep spindles (high-voltage wave bursts); arousal is more difficult
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Stage 3 – sleep deepens;; theta and delta waves appear; vital signs decline; dreaming is common
Stage 4 – EEG pattern is dominated by delta waves; skeletal muscles are relaxed; arousal is difficult
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REM Sleep Presence of beta activity (desynchronized EEG pattern)
Physiological arousal threshold increases Heart-rate quickens Breathing more irregular and rapid Brainwave activity resembles wakefulness Genital arousal Loss of muscle tone (paralysis) Vivid, emotional dreams May be involved in memory consolidation
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REM Dreaming NREM Dreaming “vivid and exciting” “just thinking”
~3 per night Longer, more detailed Fantasy world nightmares “just thinking” Shorter, less active Logical, realistic
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Dream theories Activation synthesis theory Continual activation theory
Sensory experiences are fabricated by the cortex as a means of interpreting signals from the PGO activity. Continual activation theory Encoding of short term into long-term memories. NREM sleep processes the conscious-related memory (declarative memory), REM sleep processes the unconscious related memory (procedural memory). Dream theories
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Sleep Disorders insomnia sleep walking, talking, and eating
nightmares and night terrors narcolepsy sleep apnea IM: Activity Handout 6.2: Which Sleep Disorder Is It? 30
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Sleep Disorders Insomnia: persistent problems in falling asleep, staying asleep, or awakening too early Sleep Apnea: repeated interruption of breathing during sleep Narcolepsy: sudden and irresistible onsets of sleep during normal waking hours
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Sleep disorders Nightmares: anxiety-arousing dreams occurring near the end of sleep, during REM sleep Night Terrors: abrupt awakenings from NREM sleep accompanied by intense physiological arousal and feelings of panic
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Sleep Disorders Somnambulism…sleepwalking
40% of children will have an episode, peaking at between years of age; Can be induced if arouse children during NREM; associated with complete amnesia, Occurs within 2 hours of falling asleep.. EEG..reveals both waking and sleep signals. Considered benign.
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