Circadian rhythms

What did the Mammoth Cave experiment show about humans in total darkness

Their bodies still kept a roughly 24-hour rhythm

What happened to sleepiness in the Mammoth Cave experiment

People still became sleepy at predictable times

How did body temperature behave in the Mammoth Cave experiment

It continued to rise and fall on an ~24-hour cycle

What happened to sleep patterns in the Mammoth Cave experiment

Sleep patterns stayed consistent

What major discovery came from the Mammoth Cave experiment

Humans have an internal biological clock that runs without external cues

What does shift work force people to do

Stay awake during their biological night

Why can’t the circadian clock fully adapt to night-shift work

Core body temperature, alertness, and hormones stay aligned to daytime

What does circadian misalignment cause in shift workers

Reduced attention, slower reaction times, and more health problems

What long-term risks increase with chronic circadian disruption

Metabolic disease, obesity, cardiovascular issues, and mood disorders

What does light exposure at night do to melatonin

It suppresses melatonin and makes daytime sleep lighter and fragmented

How does the WHO classify long-term shift work

A Group 2A probable carcinogen due to circadian disruption

What is circadian rhythm

An ~24.2-hour internal biological clock controlling physiological and behavioral processes

Where is the master circadian clock located

In the suprachiasmatic nucleus (SCN)

What are major functions regulated by circadian rhythms

Sleep-wake cycles, hormone release, body temperature, metabolism, immunity, cognition

What are zeitgebers

Environmental cues such as light, meals, and activity that synchronize the circadian clock

How does the circadian clock function without cues

It runs autonomously but drifts without daily light exposure

How long does the human circadian rhythm naturally run

About 24.2 hours

Where is the SCN located in the brain

In the anterior hypothalamus above the optic chiasm near the third ventricle

How does light reach the SCN

Through the retinohypothalamic tract from the eyes

What does the SCN synchronize

All peripheral clocks in organs and tissues

What hormone peaks in the morning under SCN control

Cortisol

What hormone rises at night under SCN control

Melatonin

When is core body temperature lowest

Around 4 AM

When is core body temperature highest

Around 6 PM

What causes jet lag

A sudden shift in zeitgebers like the light-dark cycle

What keeps the circadian clock aligned each day

Morning light exposure

What is a chronotype

An individual’s natural sleep timing preference

What is a morning lark

A person who prefers earlier bed and wake times

What is a night owl

A person who prefers later bed and wake times

Why do teenagers stay up later naturally

Their circadian clock is biologically delayed during puberty

Why do circadian rhythms matter for health

Misalignment affects mood, metabolism, immunity, learning, and long-term health

Why did circadian rhythms evolve

To anticipate Earth’s predictable 24-hour environmental changes

What evolutionary advantage does anticipation give

It allows organisms to prepare in advance, improving efficiency and survival

Why do organisms schedule different biological functions at specific times

To optimize energy use and prevent conflicts between processes

What happens when circadian rhythms are disrupted in animals

Reduced lifespan, impaired immunity, and decreased reproductive success

Why is the presence of circadian rhythms in all life forms important

It suggests clocks evolved early and provide universal biological advantages

What is entrainment

The process where zeitgebers synchronize the internal clock to the 24-hour day

What does morning light do to the circadian clock

Resets SCN timing and pulls the rhythm back to 24 hours

What does the hamster wheel experiment show under normal light-dark cycles

The hamster becomes active just before darkness and stays active during the dark phase

What happens when light timing is shifted for the hamster

Its activity rhythm undergoes a phase shift through entrainment

What happens to the hamster in constant dim light

It free-runs and becomes active slightly later each day

What does free-running in dim light prove

The hamster has an endogenous clock slightly longer than 24 hours

What biological phenomenon does the hamster experiment model for humans

Jet lag and circadian misalignment

What happens when the SCN of a hamster is lesioned

Its circadian rhythms are eliminated

What is masking in SCN-lesioned hamsters

Reflexive activity in darkness that is not a true circadian rhythm

What pattern appears in SCN-lesioned hamsters under constant dim light

Completely random activity with no rhythm

What does SCN lesion data prove

The SCN is necessary for generating circadian rhythms

How large is the SCN

About 20,000 neurons in less than 0.3 mm³

How many SCN clusters exist

Two, one on each side of the midline

What is the role of the SCN in the body

Master timekeeper coordinating all other circadian clocks

What is the correct scientific term for synchronization to light

Entrainment

What is entrainment

The process by which the internal circadian clock synchronizes to the external 24-hour light-dark cycle

How does light function in entrainment

It resets the SCN each day to align the internal clock with the environment

What cells detect light for circadian entrainment

Intrinsically photosensitive retinal ganglion cells (ipRGCs)

What photopigment do ipRGCs contain

Melanopsin

How are ipRGCs different from rods and cones

ipRGCs detect overall light levels, not images or colors

Why can some blind people still entrain to light

Their melanopsin-containing ipRGCs remain intact

What pathway carries light signals to the SCN

The retinohypothalamic tract

Why does the retinohypothalamic tract bypass visual pathways

Circadian timing does not require image processing

What does the SCN do with light information

Adjusts and resets the circadian clock

What does the SCN synchronize

All peripheral clocks in the body

What can influence peripheral clocks besides the SCN

Behaviors such as feeding times

What is the dominant zeitgeber for the SCN

Light

What does the SCN coordinate through output signals

Sleep-wake cycles, body temperature, hormones, metabolism, blood pressure

What did hamster experiments show about entrainment

Light signals reset the SCN to shift activity rhythms

Why couldn’t SCN-lesioned hamsters maintain a rhythm

They had no internal clock to receive light information

What is melatonin

A hormone produced by the pineal gland only at night

What does melatonin signal to the body

That it is nighttime

What does melatonin do to body temperature

Lowers it at night

When are melatonin levels lowest

During the day

When do melatonin levels peak

Around 2–4 AM

When does melatonin typically rise in the evening

Around 9–10 PM

How does the SCN control melatonin production

It inhibits the pineal gland when light is present

What happens to melatonin production in darkness

Inhibition lifts and the pineal gland produces melatonin

What role does melatonin play for the body

Broadcasts nighttime information to organs

How does the SCN act in melatonin regulation

As a gate that light closes and darkness opens

What is the primary feedback loop in the molecular clock

The CLOCK–BMAL1 activation of Per and Cry followed by PER–CRY inhibition of CLOCK–BMAL1

What does CLOCK–BMAL1 do

Activates transcription of Per and Cry genes

What happens after Per and Cry are transcribed

PER and CRY proteins are produced in the cytoplasm

What modifies PER and CRY proteins after translation

Phosphorylation by kinases such as CK1δ/ε

What does phosphorylation control for PER/CRY

Stability, degradation, and nuclear entry timing

Why does phosphorylation create delay in the clock

PER/CRY need hours to accumulate, dimerize, and enter the nucleus

What is the main function of PER–CRY complexes

Inhibit CLOCK–BMAL1 in the nucleus

What allows a new circadian cycle to start

PER–CRY degradation removes inhibition of CLOCK–BMAL1

Why does the molecular clock take ~24 hours

Multiple delays in transcription, translation, transport, complex formation, and degradation

When are Per and Cry turned on

Morning and early day

When do PER–CRY complexes enter the nucleus

Evening and night

What happens during the night phase of the feedback loop

PER–CRY inhibit CLOCK–BMAL1 and shut off Per/Cry transcription

When does PER–CRY degradation occur

Late night and early morning

How does light reset the molecular clock

Light activates retinal cells → SCN → signaling pathways → CREB phosphorylation → boosts Per transcription

What is the purpose of the secondary feedback loop

To stabilize and fine-tune the circadian clock

What do REV-ERB and ROR regulate

BMAL1 levels

Which protein turns Bmal1 ON

ROR

Which protein turns Bmal1 OFF

REV-ERB

What is the main timing loop of the circadian clock

The PER/CRY loop

What do Per1 mutant mice show in constant darkness

A shorter free-running period

Why can Per1 mutants still entrain to light

Light still resets the SCN

What does Per1 deficiency do to the internal clock

Makes it run faster than 24 hours

What is FASPS

A rare inherited circadian disorder with an advanced sleep schedule

What is the inheritance pattern of FASPS

Autosomal dominant