1. Sleep

2. Why Do We Need Sleep? Adaptive Evolutionary Function
safety
energy conservation/ efficiency
Restorative Function
body rejuvenation & growth
Brain Plasticity
enhances synaptic connections
memory consolidation

4. The ascending arousal system promotes wakeB. 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

5. Hypocreatin (orexin)

7. Sleep/Waking “Flip-Flop”
vlPOA= ventrolateral preoptic area
ACh = acetylcholine
NE = norepinephrine
5-HT = serotonin

8. Narcolepsy VS Insomnia

9. 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].

11. 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.

13. Coffee

14. Coffee
During waking, brain consume ATP

15. Coffee
During waking, brain consume ATP
adenosine

16. Coffee During waking, brain consume ATP adenosine
Adenosine bind to A1 receptor
Inhibit acetylcholine neurons

17. Coffee During waking, brain consume ATP adenosine
Adenosine bind to A1 receptor
Inhibit acetylcholine neurons
Caffeine and Theophylline are A1 antagonist

18. Sleep stages
Awake
Stage 1
Stage 2
Stage 3
Stage 4
Slow wave sleep

19. Sleep stages Awake Stage 1 Stage 2 Stage 3 Stage 4
Rapid eye movement sleep (REM)
Slow wave sleep
(NREM)

20. EEG waves

21. EEG Electrode Placement

22. 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

23. 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

24. 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

26. 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

28. 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

29. 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

30. 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

31. 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

32. 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

33. 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.