MCB 170: Circadian Rhythms and Sleep

What is the definition of circadian rhythms?

coordinating behaviors according to the daily cycles of daylight and darkness that result from the spin of the Earth

How was the circadian clock discovered?

the Jacques plant experiment

What is the Jacques plant experiment?

• plants are put into a box (so without sunlight)

• leaves open and close even without sunlight

• daily rhythms of leave movements are independent of daily sunlight

• shows an internal biological clock

What is the definition of an actogram?

a graphical representation of activity patterns

In regard to recordings of circadian rhythms, what occurs when the mice are placed in continuous darkness?

• mice are in free-running mode

• animals start earlier and earlier

• cycle is shorter than 24 hours

What are the three characteristics of circadian rhythms?

cyclic, self-sustaining, and entrainable

What are components of the cyclic characteristic?

• period of 24 hours

• Zeitgeber cues (environmental time cues)

What is the primary environmental/Zeitgeber cue?

light

What are the components of the self-sustaining characteristic?

• free-running rhythm

• phase drift

What is a free-running rhythm?

in the absence of any external Zeitgeber, activity patterns cycle with an endogenous period

What is a phase drift?

moving out of the 12 hour day/light phase

What happens during the entrainable characteristic?

circadian rhythms restore when external cues are reintroduced

What is important to know about the cave study?

• circadian rhythm changed from 24 hours to 48 hours

• 36 hours of activity and 12 hours of sleep

What is considered the “master pacemaker”?

the suprachiasmatic nucleus

Where is the suprachiasmatic nucleus (SCN) located?

the hypothalamus

What is the function of the suprachiasmatic nucleus (SCN)?

generates internal circadian rhythms in gene expression, electrophysiology, and hormone secretion to affect the function of peripheral organs

Where does the direct projection of the retina go?

to photosensitive retinal ganglion cells (RGCs)

What do the retinal ganglion cells do?

transfer information about light and darkness to the suprachiasmatic nucleus (SCN)

What does the SCN do after the RGCs transfer infromation to this area?

the SCN synchronizes rhythms with the external environment

Where do the SCN output axons go to? (5)

other parts of the hypothalamus, hippocampus, cortex, brain stem, and cerebellum

What is central-peripheral synchrony?

normal circadian rhythm

What are the causes of desynchrony?

shift work, jetlag, social jetlag, and abnormal food timing

What is central-peripheral desynchrony?

circadian misalignment

What can central-peripheral desynchrony cause?

predisposition to digestive and metabolic diseases such as metabolic syndrome + obesity, liver diseases, and GI carcinogens

Where do circadian clocks exist?

in all major organs, tissues, and cells

What are the seven CLOCK genes?

CLOCK, BMAL1, CRY, PER, REV, ROR, and CCG

What are the elements in the transcriptional-translational negative feedback loop?

• positive elements

• negative elements

• stabilizers

What is the process that the circadian genes undergo at night?

1. BMAL1 + CLOCK activates the expression of CRY + PER genes

2. CRY + PER form complexes to inhibit the activity of BMAL1 + CLOCK

3. Leads to the degradation of PER and CRY

What is the process that the circadian genes undergo in the morning?

1. REV negatively regulates the expression of BMAL1 and ROR positively regulates the expression of BMAL1

2. the BMAl1 complex regulates the expression of CCG

What is the function of CCG?

modulates essential physiological processes

What is important to know about the study on circadian oscillations of clock genes?

• researchers fused luciferase with the PER gene

• Bright signal when PER gene is transcribed

• PER bioluminescence recording from mouse SCN neurons showing synchronized oscillations

In regard to the study about mutations of the CLOCK gene, what is important to know about the wild-type mice?

• contains no mutant gene

• 12 hour day and 12 hour night cycle

• 23.6 hour period

In regard to the study about mutations of the CLOCK gene, what is important to know about the heterozygous mice?

• has one allele that contains the mutated gene

• under free-running mode

• driven by internal clock

• 24.8 hour period

In regard to the study about mutations of the CLOCK gene, what is important to know about the homozygous mice?

loss of circadian rhythmicity

What does a mutation to the CLOCK gene cause?

lengthens circadian period and abolishes the persistence of rhthmicity

What is the definition of circadian rhythms?

physiological processes that vary around the 24 hour day—including activity, alertness, hormone secretion, organ physiology, and gene expression

What is the definition of sleep?

a readily reversible state of reduced responsiveness to, and interaction with, the environment

What are two theories of sleep?

restoration and adaptation

What is the restoration theory of sleep?

sleep is for resting and recovering

What is the adaptation theory of sleep?

sleep is to keep out of trouble and hide from predators

What is the definition of an EEG?

a measurement of generalized activity of the cerebral cortex

What does EEG amplitude measure?

the synchronous activity of neurons

What do EEG rhythms often correlate with?

particular states of behavior

What is the Non-REM stage?

the stage where an idling brain is in a moveable body

When does sleep walking usually occur?

during Non-REM sleep

What is the REM sleep stage?

the stage with an active, hallucinating brain in a paralyzed body

What stage does dreaming usually occur at?

the REM stage

What are the brain waves for being awake?

low amplitude and high frequency brain waves

What is occurring stage one of the sleep cycle?

the person is starting to fall asleep

What are the brain waves like during stage 1?

low amplitude and high frequency (lower frequency than when awake) brain waves

What occurs during stage 2 of the sleep cycle?

sleep spindles

What are sleep spindles?

bursts of brain activity

What are the brain waves like during stage 2?

high frequency and high amplitude for a few seconds at a time

What state of sleep is stage 3 + 4 considered?

deep sleep

What are the brain waves like for stage 3 and 4?

high amplitude and low frequency

What stages does sleep walking occur at?

stages 3 and 4

What stages do night terrors occur?

stages 3 and 4

What stages of the sleep cycle are considered “slow wave sleep”?

stages 3 and 4

What are the brain waves like during REM sleep?

low amplitude and high frequency

At what stage of the sleep cycle are the conditions similiar to when awake?

the REM stage

How is sleep characterized?

the cyclic occurrence of non-REM sleep and REM sleep

What happens during REM sleep?

• increased eye movement

• increased heart rate

• increased respiratory rate

• increased penile reaction

• decreased muscle tone

What is the modulatory system of wakefulness/sleep?

neurons project all over the brain and release many different neurotransmitters

During wakefulness, which neurotransmitters do neurons release?

• acetylcholine

• norepinephrine

• serotonin

• histamine

• orexin

During REM sleep, which neurotransmitters are not released? (2)

norepinephrine and serotonin

During REM sleep, which neurotransmitter is released?

acetylcholine

During non-REM sleep, the activity of neurons releasing which neurotransmitters are decreased?

• acetylcholine

• norepinephrine

• serotonin

When dreaming, where is there increased neuronal activity?

• brain stem (midbrain + pons)

• limbic system (amygdala + hippocampus)

• thalamus

• visual cortex

When dreaming, where is there decreased neuronal activity?

the PFC (prefrontal cortex)

What is the dreaming process?

1. neuronal activity in the brain stem activates the thalamus + visual cortex to generate information

2. dopaminergic neurons in the VTA activate the limbic system and induce strong emotions

What is important to know about REM Sleep Behavior Disorder?

• caused by a disruption in the brain stem

• person dreams and acts them out

• dreams may not be logical due to the low PFC function

What is the Two-Process Model of Sleep Regulation?

sleep regulation has two components: process S and process C

What occurs during process S?

the build-up of homeostatic sleep drive

What occurs during process C?

circadian altering signals

What do the interaction of process S and process C generate?

the timing of sleeping and waking

What is the activity of process C throughout the day?

• low in the morning and builds up throughout the day

• goes down during sleep

What is the activity of process S throughout the day?

• low in the morning and builds throughout the day

• goes down during sleep

When is there a dip in energy levels?

early afternoons

What are the two molecules of the sleep drive?

adenosine and melatonin

When is the amount of adenosine increased?

builds up in the brain during wakefulness due to energy consumption; during the day

What blocks adenosine?

caffeine

What is melatonin?

a hormone secreted by the pineal gland in the brain

What is the function of melatonin?

helps maintain daily schedule of sleeping and waking

What inhibits melatonin?

daylight

How is melatonin production regulated?

1. the SCN, via an inhibitory projection to the paraventricular nucleus of the hypothalamus, controls the sympathetic output to the pineal gland that is responsible for melatonin secretions

2. the presence of the light activates SCN neurons to inhibit the secretion of melatonin

2. darkness suppresses the SCN inhibition and facilitates the secretion of melatonin

What does deep sleep promote?

memory consolidation

What is important to know about the deep sleep study and the odor?

• re-exposure to the odor during slow wave sleep, but not REM sleep, enhanced the spatial memories and induced stronger hippocampal activation than during wakefulness

• reactivation of memory traces occurs during slow wave sleep

What does sleep deprivation do?

alternates vigilant attention and severely compromises the ability of human beings to respond to stimuli in a timely fashion

What areas can be impacted due to sleep deprivation?

• fatigue

• anxiety

• learning and memory

• decision making

• immune system

• risk of obesity

What are the positive elements of the negative feedback loop?

CLOCK and BMAL1

What are the negative elements of the of the negative feedback loop?

CRY and PER

What are the stabilizers of the negative feedback loop?

REV and ROR