Modulating Arousal: Circadian Rhythms Humans have a natural daily rhythm that is just slightly longer than 24 hours This daily rhythm is largely modulated by the suprachiasmatic nucleus The SCN generates our circadian rhythms in a genetically- controlled manner. It continues to fire according to a daily rhythm even it is removed from the body!

How does the SCN operate? The role of light: Light, transmitted from the retina, is processed in the SCN. Blocks the activity of proteins the trigger sleepiness Triggers the SCN to send a signal to the pineal gland that inhibits release of melatonin, which would normally trigger sleepiness.

How does the SCN operate? The role of light: A lack of light, therefore, leads to melatonin release. Melatonin levels increase considerably roughly 2-3 hours before sleep Melatonin increases sleepiness. Also helps to “reset” the biological clock by feeding back to the SCN

Circadian rhythms also affected by adenosine Adenosine is a byproduct of ATP usage It builds up during waking periods, when ATP use is high High levels of adenosine inhibit basal forebrain activity and induce sleepiness Adenosine levels fall during sleep, allowing basal forebrain to produce behavioral arousal and wakefulness DAY NIGHT SLEEP 6 am 6 pm Adenosine concentration

Receives input from brainstem and hypothalamus Activated by orexin (hypocretin) Activated by orexin (hypocretin) Also stimulated by caffeine Also stimulated by caffeine Basal forebrain Releases acetylcholine –This neurotransmitter produces arousal and wakefulness –When you are asleep, this neurotransmitter triggers the transition from stages of sleep that are less mentally active (nREM) to stages that are more mentally active (REM) Brain Mechanisms of Arousal: Basal Forebrain

Why does caffeine prevent sleep? Activation of the basal forebrain increases arousal Adenosine inhibits activity in basal forebrain Supplements of adenosine promote sleepiness Antagonists of adenosine, like caffeine, promotes arousal and alertness

Brain Mechanisms of Arousal: Locus Coeruleus Stress-Center: responds to important, meaningful events by releasing norepinephrine Norepinephrine (NE) increases brain arousal, increases attentional focus and promotes memory.

Why does alcohol induce sleep? Alcohol is an agonist of GABA (the brain’s main inhibitory neurotransmitter) How does GABA influence sleep? Decrease activity of cortical neurons by decreasing the strength of EPSPs GABA activity is higher during “deeper” stages of sleep.

Purpose of sleep: Repair & Restoration During sleep -Brain rebuilds proteins and energy reserves -White blood cell activity increases -Growth hormone levels increase -Brain activity appears to “replay” important information from previous waking period. -Appears brain also “discards” unimportant information that was recently encountered Some research has suggested that long term sleep deprivation is deadly because body cannot repair itself and protect itself from infection sleep deprivation

Sleep stages

EEG recording during sleep Awake: alpha rhythm Stage 2: Sleep spindles & K-complexes appear Stages 3/4 delta rhythms

REM vs nREM sleep -Presence of dreams -Paralysis of limbs -Brain activity -Ease of waking -Nature of HR, BP and breathing -Presence of sexual arousal -Contributions to learning/memory and body repair

Functions of REM Sleep Brain development Brain development In utero, fetus begins REM sleep around 30 weeks and peaks at 40 weeks; infants spend majority of time asleep and 70% in REM. In utero, fetus begins REM sleep around 30 weeks and peaks at 40 weeks; infants spend majority of time asleep and 70% in REM. “Reverse learning” –Some have suggested sleep is necessary dissolve the storage of information that is not useful Memory consolidation –Seems to be especially important for consolidating the memory of new and important information –Destroying the brainstem neurons that produce theta rhythms causes memory deficits for recently learned skills

Should employers limit the number of hours employees are allowed to work? Should employers limit the number of hours employees are allowed to work? Surgeons? Surgeons? Truck driver? Truck driver? Airline pilots? Airline pilots? Should schools have classes that start at 8 am? link Should schools have classes that start at 8 am? link link

What are dreams and what purpose might they serve?

Brain activity during REM sleep PGO waves start in the pons (P) and then show up in the lateral geniculate (G) and the occipital cortex (O). Each PGO wave is synchronized with an eye movement in REM sleep. PGO waves activate regions in cortex and limbic system Results in activation of stored memories (long term and recent) Activation of amygdala gives dreams strong emotional content

Brain activity during REM sleep PGO waves start in the pons (P) and then show up in the lateral geniculate (G) and the occipital cortex (O). Each PGO wave is synchronized with an eye movement in REM sleep. The prefrontal cortex is usually inhibited Therefore, dreams lack proper reasoning or planning since interpretation of sensory activity is unconstrained The pons inhibits the spinal cord from sending messages to motor neurons- we are paralyzed!

Role of thalamus in dreaming and regulating sleep During REM sleep, a different pattern of brain waves is observed This activity appears to promote sensory input to cortex and limbic system This creates the sensory experiences we call dreams During non-REM sleep, certain thalamic nuclei create slow, synchronized waves This activity appears to block the flow of sensory information to the cerebral cortex

What happens during insomnia? Insomnia is a relatively common experience. One third of people experience insomnia at some point in their lives. Causes: Emotional Stress, anxiety, worry Depression and other mood disorders Physical Chronic medical conditions Medications (anti-depressants, allergy medications) Food/Drink (caffeine, cigarettes, heavy or spicy foods Problems with sleep routine and/or sleep environment

What happens during insomnia? Treatments For chronic sufferers, medications (including Ambien) have typically targeted the neurotransmitter GABA. For chronic sufferers, medications (including Ambien) have typically targeted the neurotransmitter GABA. While these medications are effective, they have a number of side effects, including potential memory problems While these medications are effective, they have a number of side effects, including potential memory problems Newer treatments being tested target the specific neurochemicals of sleep. Newer treatments being tested target the specific neurochemicals of sleep. Some treatments are designed to increase melatonin or adenosine, which each promote sleepiness) Some treatments are designed to increase melatonin or adenosine, which each promote sleepiness) Others are designed to decrease hypocretin (a protein that stimulates arousal). Others are designed to decrease hypocretin (a protein that stimulates arousal).

Why do some allergy medicines make you sleepy? -Many allergy medicines are anti-histamines, meaning that they block the activity of histamines in the body - A histamine response is the body’s immune response to some substance (pollen; dust) that is not harmful. It is a “mistake”. - However, the body always has some histamine and this neurotransmitter acts on the hypothalamus to promote arousal -Blocking histamine will decrease arousal and make you sleepy