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

DAYNIGHT

SLEEP6 am

6 pm

Adenosine concentration

Receives input from Receives input from brainstem and brainstem and hypothalamushypothalamus

Activated by orexin Activated by orexin (hypocretin)(hypocretin)

Also stimulated by caffeineAlso stimulated by caffeine

Basalforebrain

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:Brain Mechanisms of Arousal:Locus CoeruleusLocus 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:Purpose of sleep: Repair & RestorationRepair & 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 stagesSleep stages

EEG recording during sleepEEG recording during sleep

Awake: alpha rhythm

Stage 2:Sleep spindles & K-complexes appear

Stages 3/4 delta rhythms

REM vs nREM sleepREM 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 SleepFunctions of REM Sleep Brain developmentBrain development

In utero, fetus begins REM sleep around 30 In utero, fetus begins REM sleep around 30 weeks and peaks at 40 weeks; infants spend weeks and peaks at 40 weeks; infants spend majority of time asleep and 70% in REM.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 Should employers limit the number of hours employees are allowed to of hours employees are allowed to work?work? Surgeons?Surgeons? Truck driver?Truck driver? Airline pilots?Airline pilots?

Should schools have classes that Should schools have classes that start at 8 am? start at 8 am? linklink

What are dreams and what What are dreams and what purpose might they serve?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?What happens during insomnia?Insomnia is a relatively common experience. Insomnia is a relatively common experience. One third of people experience insomnia at One third of people experience insomnia at some point in their lives.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?What happens during insomnia?

TreatmentsTreatments For chronic sufferers, medications For chronic sufferers, medications (including Ambien) have typically (including Ambien) have typically targeted the neurotransmitter GABA. targeted the neurotransmitter GABA.

While these medications are effective, While these medications are effective, they have a number of side effects, they have a number of side effects, including potential memory problemsincluding potential memory problems

Newer treatments being tested Newer treatments being tested target the specific neurochemicals of target the specific neurochemicals of sleep. sleep.

Some treatments are designed to Some treatments are designed to increase melatonin or adenosine, which increase melatonin or adenosine, which each promote sleepiness) each promote sleepiness)

Others are designed to decrease Others are designed to decrease hypocretin (a protein that stimulates hypocretin (a protein that stimulates arousal).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