Chapter 14: Biological Rhythms

Why do we have circadian rhythms?

because life evolved on a planet with predictable environmental changes

• organisms that can anticipate and plan for these occurrences are advantaged over those unable to do so 

What determines the light and dark pattern to which we are exposed?

earth’s yearly revolution around the sun and its daily rotation on its axis 

What are the 3 levels rhythms may be?

1. behavioral

2. physiological

3. biochemical

Circadian Rhythms

functions of a living organism that display a rhythm of about 24 hours

Ultradian Rhythms

referring to a rhythmic biological event with a period shorter than that of circadian rhythm usually from several minutes to hours long and occurs more than once per day

• period of less than 20 hours

• ex. heart rate 

Infradian Rhythms

rhythms occur less than once per day

• period of greater than 28 hours

• weeks, months, years

• ex. menstrual cycle 

There is a flower that blooms every 100 years. Neural rhythms can occur every millisecond.

What does this say about biological rhythms?

range of periods of biological rhythms extends from milliseconds to cycles greater than 100 years 

Dinural

active during light periods of daily cycle

Nocturnal

active during dark periods of daily cycle

Circadian rhythms are generated by an (1) _____ (internal) clock

(1) endogenous 

Free-Running

animal is maintaining its own cycle with no external environmental cues such as light 

Period

the interval of time between 2 similar points of successive cycles 

• may not be exactly 24 hours

• ex. sunrise to sunset 

Phase Shift

the shift in activity in response to a synchronizing stimulus such as light or food

Entrainment

the process of synchronizing a biological rhythm to an environmental stimulus 

Zeitgeber

“time-giver”; exogenous (external) cue that synchronizes an organism’s endogenous (internal) time-keeping system (clock) to the earth’s 24 hour light/dark cycle

• entrains circadian rhythms

What is the most potent zeitgeber for circadian rhythms?

light 

Do rhythms persist in the absence of zeitgeber?

yes; free-running animals

Exogenous Rhythms

rhythms that are generated as a result of processes occuring outside the organism 

• ex. seasonal allergies; occur because of pollen 

Endogenous Rhythms

rhythms that arise as a result of processes occurring within the organism 

What is the neurological basis for endogenous circadian rhythms?

suprachiasmatic nuclei

Suprachiasmatic Nuclei

biological clock; small region of the hypothalamus above the optic chiasm 

What are the effects of SCNx?

disrupted circadian rhythms 

T or F: Isolated SCNs are non-functional

false- isolated SCNs can maintain electrical activity synchronized to the previous light cycle

Hamsters with abolished circadian rhythms received SCN tissue transplants from hamsters with a 20 hour period. 

Circadian rhythms were restored but matched the shorter period of the doner. 

What does this tell us?

proves that the endogenous period is generated in the SCN 

How can circadian rhythms entrain to light-dark cycles?

using different pathways- some outside of the eye 

How do circadian rhythms in amphibians and birds entrain to light-dark cycles?

pineal gland is sensitive to light (third eye)

How do circadian rhythms in mammals entrain to light-dark cycles?

light info goes from the eye to the SCN via the retinohypothalamic pathway 

Retinohypothalamic Pathway 

the projection of retinal ganglion cells to the SCN 

• many of these retinal ganglion cells contain melanopsin 

Do the ganglion cells in the retinohypothalamic pathway have rods and cones?

no

Melanopsin

special photopigment in retinal ganglion cells that makes them sensitive to light

If light hitting the eyes provides entrainment info to the pacemaker then lesions of the visual projections to the brain should abolish entrainment.

Lesions of the primary optic tract result in perceptually blind animals that entrain perfectly to light dark cycles.

What can we conclude from this about the relationship between the retinohypothalamic pathway and vision?

the retinohypothalamic pathway is not the same visual pathway that is responsible for the classic visual system 

What does the following indicate?:

In vitro, adrenal tissue displayed corticosterone rhythms.

non-SCN oscillators/self-sustaining clocks exist within the body

What does the following indicate?:

Arrhythmic SCNx rats given methamphetamine display free-running locomotor activity.

non-SCN oscillators/self-sustaining clocks exist within the body; one perhaps driven by meth

What does the following indicate?

Animals with SCNx still display food anticipatory behavior (FAA).

non-SCN oscillators/self-sustaining clocks exist within the body; food entrained oscillator (FEO) 

• synchronized by timing of meals 

T or F: Each cell knows when 24 hours have passed/has its own clock.

true

SCN cells in mammals make what 2 proteins?

1. clock

2. cycle 

What do clock and cycle proteins do?

they form a dimer which promotes transcription of period (per) and cryptochrome (cry) genes

Per, Cry, and Tau protein complex enters the nucleus and inhibits the transcription of per and cry.

No new proteins are made until first set degrades and cycle begins gain.

What is this an example of?

negative feedback loop 

Dimer

complex of two proteins bound together

What gives cells the ability of sense the passage of 24 hours?

the negative feedback loop of the molecular clock- the cycle/loop takes 24 hours 

How does light entrain the molecular clock in flies?

light reaches brain directly and degrades clock protein

How does light entrain the molecular clock in mammals?

retinal ganglion cells detect light and release glutamate in the SCN

• glutamate triggers events that promote production of the Per protein, which in turn, shifts the clock and the animal’s behavior 

What happens in Tau mutations?

period is much shorter than normal

What happens when double clock mutants are produced?

organism is able to entrain but under constant conditions displays arrhythmicity 

What external events/stimuli is sleep synced to?

stimuli like light, food, jobs, and alarms entrain us to be asleep or awake

In the absence of external cues, what happens to human sleep?

humans have a free-running period of about 25 hours 

• varies with age 

Human males produce more testosterone in the morning and have a dip mid-day.

What does this say about the rhythms humans display?

humans exhibit circadian rhythms in hormone secretion 

Humans are able to better metabolize alcohol in the evening, displaying increased blood-alcohol levels under the same dosage when taken in the morning.

What does this say about the rhythms humans display?

humans exhibit circadian rhythms in physiological function 

• drug metabolism 

There are higher rates of women losing their virginity in summer months. 

What does this say about the rhythms humans display?

humans exhibit seasonal rhythms in behavior 

T or F: Humans consistently show endogenous rhythms.

false- humans rarely show endogenous rhythms

• biological and behavioral rhythms highly influenced by external stimuli

The following are displayed in humans in what kind of rhythm?:

• Birth 

• Morality 

• Depression 

• Suicide 

• Hormone Secretion 

• Cellular Immune Function 

• Diet 

• Sudden Infant Death Syndrome 

seasonal rhythm

What are the two distinct classes of sleep?

1. slow-wave sleep (SWS)

2. rapid eye movement (REM)

Slow-Wave Sleep (SWS)

can be divided into 4 stages and is characterized by slow wave EEG activity

Rapid-Eye-Movement Sleep (REM)

characterized by small amplitude, fast EEG waves, no postural tension, and rapid eye movements

Do mammals sleep more in infancy or adulthood?

infancy

What is infant sleep characterized by?

• shorter sleep cycles

• more REM sleep- 50%, which may provide essential stimulation to the developing nervous system

Why is babies’ sleep arrhythmic in the first few weeks after birth?

the SCN is not yet developed

Why is babies’ sleep free-running from about week 9-16 after birth?

SCN has developed but retinohypothalamic tract has not developed

What are babies called around 16 weeks after birth when they begin to sleep through the night?

entrained

Answer the following about a typical night of young adult sleep:

What is the average sleep time?

7-8 hours

Answer the following about a typical night of young adult sleep:

How much time is spent in each phase?

45-50% of the time is sleep stage 2 (SWS), 20% is REM

Answer the following about a typical night of young adult sleep:

How long do cycles last and what stages are most prevalent?

cycles last 90-110 minutes but cycles early in the night has more stage 3 and 4 SWS and later cycles have more REM

During puberty most people shift their circadian rhythm so….

they get up later in the day

When high schools implemented later start times what happened to attendance, enrollment, and depression rates?

later starts improved attendance and enrollment and reduced depression and in-class sleeping

As people age what happens to total time asleep and number of awakenings?

total time asleep declines and number of awakenings increases

At 60 only half as much time is spent in sleep stages 3 and 4 as at 20- by 90 stages 3 and 4 disappear.

What does this say about sleep changes in elderly sleep?

the most dramatic decline is in the loss of time spent in stages 3 and 4

Sleep Deprivation

the partial or total prevention of sleep

What are the effects of sleep deprivation?

• increased irritability

• difficulty concentrating

• episodes of disorientation

* effects can vary with age and other factors

T or F: Total sleep deprivation compromises the immune system and leads to death.

true

Fatal Familial Insomina

an inherited disorder in which humans normally sleep when young but stop sleeping in midlife and die 7-24 months later

What is the clinical relevance for studying circadian rhythms?

diseases are linked to circadian rhythms

Why can shift work have a negative impact on health?

forcing diurnal animal to be nocturnal

What are the following resulting from?:

• Interferences with work performance and efficiency over 24 hour span with consequent errors and accidents

  • learning and memory deficits

  • slowed reaction time

  • reduced vigilance

• Difficulties in maintaining usual relationships (family and social) with consequent negative influences on marital relations, social contact, and care of kids

  • higher alcohol consumption

• Deterioration of health that can be manifested in sleep and eating disturbances and in the long run severe disorders

  • exacerbation of pre-existing psychiatric disorders

  • reduced sleep efficacy

  • type 2 diabetes

  • cardiovascular problems

  • obesity

  • ulcers

  • depression

shift work and the sleep deprivation/circadian interferences it causes

What are some of the severe disorder that can manifest from shift work and the circadian interferences it causes?

• gastrointestinal (colitis, peptic ulcer, gastroduodenitis)

• neuro-physic (chronic fatigue, anxiety, depression)

• cardiovascular (hypertension, ischemic heart diseases)

What happens to the brain when exposed to chronic jetlag?

temporal lobe (hippocampal) atrophy and cortisol alterations

T or F: There are decreased cancer rates in shift workers.

false- there are increased rates of cancer among shift workers because cells divide faster at different times of day

Chronopharmokinetics

study of how physiological rhythms (primarily CR) influence the way the body handles drugs

• includes ADME (absorption, distribution, metabolism, and elimination)

ADME

absorption, distribution, metabolism, and elimination

• vary markedly throughout the day

T or F: Time of day affects the body’s ability to metabolize drugs leading to more steady absorption rates when taken at the correct time.

true

When using chronotherapy instead of traditional chemotherapy what results can be seen?

doubled survival rates and cut severity of symptoms/treatment complications in half

Why are there daily changes to sensitivity to chemotherapy?

• drug toxicity

  • most effective at time of least toxicity

  • higher doses can be tolerated at time of least toxicity

• daily changes in catabolic enzyme of cancer drugs

• daily change in mitotic index of carcinoma cells

In a cancer patient, if cells are dividing more in the morning than at night, when should you provide chemotherapy?

the morning

Seasonal Affective Disorder (SAD)

annual depression in late fall and winter in temperate zones

• late fall onset and spontaneous remission in spring

• age of onset: 20

• more common in women

What are the symptoms of seasonal affective disorder?

• sadness

• anxiety

• premenstrual difficulties

• decreased energy, activity, and libido

• hypersomnia

• increased appetite especially for carbs

• increased body weight

• difficulties with work and relationships

What does seasonal affective disorder increase in severity with?

distance from the equator in temperate zones

• most severe in January/February with spontaneous recovery after vernal equinox

Answer the following regarding light treatment claims:

T or F: It works more rapidly than antidepressants but its biological basis is unknown.

true

Answer the following regarding light treatment claims:

What types of light is most effective- bright or dim, morning or evening, long or short duration?

• bright

• morning

• long duration

Answer the following regarding light treatment claims:

T or F: UV is needed for the light to be most effective.

false- visible portion of spectrum works; do not need UV

Answer the following regarding light treatment claims:

T or F: Depression can be triggered by 1-2 days of overcast.

true

Answer the following regarding light treatment claims:

T or F: Light is mediated by the skin.

false- light is mediated by the eyes

What are examples of shorter (ultradian) biological rhythms?

• bouts of activity

• feeding

• hormone release

What are examples of longer (infradian) biological rhythms?

body weight and reproductive cycles

Circannual Clock

endogenous clock, seperate from the SCN, occuring at a roughly annual basis

Why do we have seasonal rhythms?

because life evolved on a planet with predictable environmental changes

• organisms that can anticipate and plan for these occurrences are advantaged over those unable to do so

  • e.g. fat deposition prior to hibernation

Animals typically face greater challenges in winter and autumn than in spring and summer- what is one factor that affects survival?

energy availability and the costs of its acquisition

What is the principal target of natural selection in the evolution of seasonality?

the reproductive cycle

What is the currency of natural selection?

fitness

Regarding natural selection, issuing offspring is insufficient- what else must one do?

one must issue offspring that survive to breed

How is reproduction energetically demanding for the mother and offspring?

• mother- lactation

• offspring- rapid growth

Seasonal reproduction functions to restrict breeding to certain times of year- what may this allow?

may allow “expensive” phases of life cycle to coincide with resources within the environment