生物時鐘 (Biological clocks) ─ 動物行為學 (Ethology) 鄭先祐 (Ayo) 國立臺南大學...

生物時鐘 (Biological clocks)

─ 動物行為學 (Ethology)

鄭先祐 (Ayo)

國立臺南大學環境與生態學院生態科學與技術學系教授

Ayo NUTN Web: http://myweb.nutn.edu.tw/~hycheng/

大學部生態學與保育生物學學程 ( 必選 ) 2010 年秋冬

Ayo 教材 (動物行為學 2010) 2

Part 1. 動物行為的研究途徑 ( 個體行為 )

歷史背景 (History of the Study of Animal Behavior ).

基因分析 (Genetic Analysis of Behavior ). 天擇 (Natural Selection and Behavior ). 學習與認知 (Learning and Cognition.) 生理分析 (Physiological Analysis)

( 一 ) 神經細胞 (Nerve Cells and Behavior ). ( 二 ) 內分泌系統 (The Endocrine System).

發育 (The Development of Behavior ).


Part 2. 存活 ( 與環境的互動關係 )

生物時鐘 (Biological Clocks) 導航機制 (Mechanisms of Orientation and

Navigation) 空間分佈的生態學與演化學 (The Ecology and

Evolution of Spatial Distribution) 覓食行為 (Foraging Behavior) 抗掠食行為 (Antipredator Behavior)


08 生物時鐘 (Biological clocks)

Clock-controlled rhythms Rhythmic behavior The clock versus the hands of the clock Advantages of clock-controlled behavior Adaptiveness of biological clocks Organization of circadian systems Human implications of circadian rhythms


Animals have internal clocks

Hamsters ( 倉鼠 ), as well as all other animals, have an internal, living clock Its bouts of activity

alternate with rest It is so regular that it is

described as an activity rhythm


Most animals can measure time

Biological clocks have been found in every eukaryotic organism tested As well as in cyanobacteria

The rhythmical nature makes sense in the light of evolutionary principles Ecological conditions vary tremendously at different

times of the cycle It is adaptive to predict upcoming changes in a cycle

(i.e. upcoming darkness or winter), rather than just respond to these events


Environmental modifications are extreme but predictable Biological clocks have evolved as adaptations to

environmental cycles Biological clocks also provide a mechanism to synchronize

various internal processes with other internal processes Rhythms have piqued( 引發 ) the interest of scientists studying

Their adaptive value and evolution Genetic underpinnings ( 基因基礎 ) Hormonal control Neural control


Properties of clock-controlled rhythms

Biological clocks measure time at the same rate under nearly all conditions They can be reset to remain synchronized with

environmental cycles In clock-controlled rhythms, cycles continue in the

absence of environmental cues (i.e. light-dark and temperature cycles)

Instead, the ability to keep time without external cues is due to an internal (endogenous) biological clock


Biological rhythms

The period (the interval between two identical points in the cycle) of the rhythm can become longer or shorter Circadian rhythm: a daily rhythm (24 hours in nature) Circalunidian: a lunar day (tidal) rhythm Circamonthly: a monthly rhythm Circannual: an annual rhythm

Free-running period: a circadian period length under constant conditions It is not manipulated by environmental cycles


Entrainment to environmental cycles

Biological rhythms are not exactly as long as natural cycles A light-dark cycle: the most powerful phase-setting agent in

circadian rhythms Nonphotic cues (i.e. social interactions, feeding

schedules, or temperature cycles) also play a part Manipulating the light-dark cycle resets (entrain) the

biological clock A brief light pulse during early circadian night resets

the clock In nature, the clock is reset by light at dawn and dusk

each day


Light sampling behavior resets the circadian clock

Flying squirrels are nocturnal Their circadian clock wakes them at twilight ( 薄暮 ) If it is still light outside, the squirrel returns to its nest

to sleep and its circadian clock is reset Activity begins slightly later the next night

The squirrel’s activity rhythm entrains to the light-dark cycle with only a few minutes of light exposure This phase adjustment also causes the squirrel’s onset

of activity to follow sundown as it changes through the year


Biological clocks are insensitive to temperature changes

If biological clocks were affected by changes in temperature: They would run at different rates at different times of day

Cave dwelling, insectivorous bats of the temperate zone roost in cool, deep caves during the day Their body temperature drops while resting to conserve

metabolic energy Their temperature rises when they leave the cave to forage The biological clock remains accurate


Daily rhythms

Nocturnal animals are busiest at night Hamsters, cockroaches, bats, mice, and rats

Diurnal animals are active during the day Most songbirds and humans

Crepuscular animals are active primarily at dawn and dusk


Lunar day rhythms

As the moon passes over the surface of the earth, its gravitational field draws up a bulge in the ocean waters Causing high tides when they reach the shoreline There are usually two high tides each lunar day -

one every 12.4 hours The tides cause some dramatic changes in the

environment, Particularly for organisms living on the seashore

Rhythms synchronized with tides are lunar day rhythms


Fiddler crab activity is synchronized with tidal changes

Fiddler crabs are active during low tide In search of food and mates

Before high tide, the crabs return to their burrows A fiddler crab’s behavior in the laboratory remains

rhythmic Periods of activity alternate with quiescence every 12.4

hours The usual interval between high tides


An activity rhythm of a fiddler crab (Uca pugnax). Althouth the crab was maintained in constant darkness and temperature(20 ).℃


Semilunar rhythms

The gravitational field of the sun also influences the height of the tides The highest tides are caused when the gravitational fields

of the moon and the sun operate together At new moon and full moon, the earth, the moon, and

the sun are in line The gravitational fields of the sun and the moon augment

each other


The effect of the relative positions of the earth, moon, and sun on the amplitude of tidal exchange.

(a) at the times of new and full moons,

(b) during the first and last quarters of the moon.


Spring and neap tides

Spring tides: the highest high tides and lowest low tides at new and full moons

Neap tides: periods of lowest high tides and highest low tides at the quarters of the moon

Some organisms possess a biological clock that helps them predict the times of spring or neap tides In the tiny chironomid midge, emergence of adults from

their pupal cases is programmed to coincide with tidal changes.


chironomid midge

Many species superficially resemble mosquitoes but they lack the wing scales and elongate mouthparts of the Culicidae.

This is a large group of insects with over 5000 described species and 700 species in North America alone.

Chironomidae (informally known as chironomids or non-biting midges) are a family of nematoceran flies with a global distribution.


Monthly rhythms

A synodic lunar month: the interval from full moon to full moon (29.5 days) The time it takes the moon to revolve once around the earth Some organisms can program their activities to occur at

specific times during this cycle The ant lion shows a monthly rhythm in the size of the pit it

builds Small arthropods, such as an ant, slide into the pit At full moon, it constructs larger pits This is a clock-controlled rhythm - not a response to an

environmental factor


Pit size of ant lion

A monthly rhythm in the pit size of the predatory ant lion.

Monthly rhythms in the pit size of 50 ant lions maintained in constant condition in the laboratory.


Annual rhythms

Annual biological clocks are important In timing migration To prepare animals physiologically for migration and

reproduction A garden warbler in the laboratory with constant

temperature and unvarying day length (12 hours light - 12 dark) lacks obvious seasonal cues During summer and winter months, it limits activity to

daylight hours It becomes active at night during autumn and spring, when

it would normally be migrating


Annual cycles in migratory restlessness, body weight, testis size, and molting in a garden warbler held in constant light-dark cycle and at a constant temperature.


Caged birds have zugunruhe

Zugunruhe (migratory restlessness): a cage-adapted nocturnal form of migratory activity

The timing function is very important for birds wintering close to the equator A constant photoperiod and variable rainfall and food

abundance don’t provide proper cues to signal the time to begin migrating


The annual clock affects physiology

It readies birds for migration and reproduction A bird gets fatter during winter to provide fuel for the

spring migration It molts during winter Its testes enlarge for summer reproductive activity

These cycles are free-running for many years in constant conditions The length of the cycle is slightly longer or shorter than a

year


Circadian vs. annual clocks

Seasonal changes may be controlled by a response to the changing photoperiod Shortening days during winter months and increasing

daylight of spring and summer Measuring a change in daylength requires only a

circadian clock A rhythm controlled by an annual clock continues to be

rhythmic even without changing day length


Stop and think

When one wants to determine whether a daily, tidal, or lunar rhythm is controlled by an endogenous clock, the organism is placed in constant light or constant darkness

When one wants to determine whether an annual rhythm is controlled by an annual clock, the animal is kept in a constant photoperiod

Why are the procedures different?


Anticipation of environmental change

Why time an event with a biological clock rather than responding directly to periodic environmental fluctuations? To anticipate periodic environmental changes To synchronize behavior with other events To measure an interval of time


Anticipation of environmental change

An animal can anticipate change and prepare for it Adult fruit flies emerge from their pupal cases at dawn,

when it is cool and moist They can expand their wings with a minimal loss of

water If they waited until later, water loss to the arid air could

prevent the wings from expanding properly


Synchronization of behavior

Allowing a clock to control an event allows behavior to be synchronized with a factor in the environment that cannot be sensed directly

Bees time their flights to visit flowers that are open( 開花 ) only during certain times

A bee can not use vision or olfaction to determine whether flowers far from the hive are open


Bees visit open flowers

After training, bees visited a feeding station only during learned hours

With their biological clock, bees time their visits to flowers so they arrive when the flower is secreting nectar And gather the maximum amount of food with the

minimum effort


(b) bees were trained to come to a feeding dish only at the specific times at which food was made available.

(c) after six days of training, the feeding dishes were left empty and the number of bees arriving throughout the day was recorded. The bees arrived at the feeding station only when food had been previously present.


Continuous measurement of time

Measuring passage of time is crucial to time-compensated orientation

A honeybee’s dance indicates the direction to a nectar source Telling other bees the flight bearing relative to the sun

Because the sun is a moving reference point, the honeybee’s biological clock provides the information for The time of day when it discovered the nectar How much time has passed since then


Organization of circadian systems

A complex nervous system or endocrine system is not an essential component of the biological clock Single cells, unicellular organisms and cells that make

up tissues and organs have their own independent clocks

There is no such thing as “the” biological clock Clocks are scattered throughout an animal’s body

Fruit flies have a multitude of independent clocks throughout their bodies They respond to changes in light-dark cycles without

any help from the head


Fruit flies have multiple clocks

Glow rhythms indicate per gene activity synchronizes with light-dark cycles And continue in constant darkness with a free-running

period length Separate cultures of body parts exposed to the same

light-dark cycle glow in unison( 一致、合諧 ) Each piece of cultured tissue has its own independent

clocks and these clocks have their own photoreceptors


The insect brain is not needed as a master clock

To synchronize rhythms throughout the body. Clocks in different cells run at slightly different rates

without a light-dark cycle Independent clocks gradually become asynchronous

When exposed to a new light-dark cycle, the clocks throughout the fly entrain within one cycle and the glow becomes rhythmic again

In nature, asynchrony among peripheral clocks is not a problem Fruit flies have an environmental light cycle that can

synchronize independent clocks Because each has its own photoreceptor


Animals have at least one master clock

Most rhythmic animals have multiple independent peripheral clocks throughout the body

How are an individual’s clocks synchronized so all rhythmic processes occur at the appropriate time Relative to one another and the environment’s cycles?

At least one “master” clock in the brain is entrained by the light-dark cycle It regulates other clocks through the nervous and/or

endocrine system


The master clock: the general scheme

The general scheme of circadian organization One clock or several interacting clocks function as

master clocks to synchronize peripheral clocks The output from the master clock(s) can be neural or

hormonal The clocks are set to the right time because

photoreceptors convey information on the light-dark cycle to the clock(s)

Peripheral clocks generate the rhythmic output, which may feedback on and affect the master clock(s)


The master clock: photoreceptors

What photoreceptors are responsible for entrainment? Mammalian eyes contain photoreceptors for light

entrainment These photoreceptors are in a different part of the retina

than those involved in vision Information about lighting conditions reaches the clock

through the retinohypothalamic tract (RHT) A bundle of nerve fibers connecting the retina with the

hypothalamus


The master clock: where is it?

The circadian system in mammals is a hierarchy of clocks The SCN (suprachiasmatic nucleus) is the master

biological clock Evidence that the SCN is the master clock

It is independent: SCN activity remains rhythmic in cultures Spontaneous electrical firing of individual neurons is

rhythmic in constant conditions, each of them with a slightly different period

The SCN is a self-sustaining oscillator that instills rhythmicity in other brain regions through neural connections


The master biological clock of mammals SCN

The suprachiasmatic nucleus or nuclei (SCN), is a tiny region on the brain's midline, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms. The neuronal and hormonal activities it generates regulate many different body functions in a 24-hour cycle, using around 20,000 neurons.

The SCN, pine cone shaped and the size of a grain of rice, interacts with many other regions of the brain. It contains several cell types and several different peptides (including vasopressin and vasoactive intestinal peptide) and neurotransmitters.


The suprachiasmatic nucleus (SCN) in the brain

(a) the firing rate of a single neuron from the SCN continues fo fire rhythmically in tissue culture.

(b) photoreceptors in the mammalian circadian system reach the SCN via the retinohypothalmic tract (RHT).


Nerve activity in specific brain regions (the caudate and the suprachiasmatic nuclei) of a rat before and after isolating an “island” of brain tissue containing the SCN.

The SCN instills rhythmicity


The master clock regulates other clocks

When an SCN from a conspecific is transplanted into rats or hamsters that have been made arrhythmic by destroying their own SCN Their activity becomes rhythmic once again The period length of the restored activity rhythm

matches that of the transplanted SCN The SCN is the clock that provides timing information

And not just a component needed to make the host’s clock function


The genetic basis of circadian timing

What are the molecular gears that make the clock tick? Rhythmic gene activity is involved in the clock

mechanism The products of one gene or set of genes activate or

inhibit the activity of other genes Which in turn affect the activity of the first genes Creating a self-regulated feedback loop of gene activity

measuring approximately 24 hours


The genetic basis of the circadian cycle

Two proteins—Clock and BMAL1—bind together, forming a complex that enters the nucleus

The Clock/BMAL1- complex turns on the activity of the period (per) and the cryptochrome (cry) genes The protein products of these genes (Per and Cry)

bind with the protein product of the tau gene to form a complex


The genetic basis of circadian timing in mammals consists of two feedback loops in gene activity.


A 24-hour feedback mechanism

The Per/Cry/Tau complexes suppresses action of the Clock/ BMAL1 complex Resulting in less activity of per and cry

With less Per and Cry produced and the degradation of Per, Cry and Tau The level of the Per/Cry/Tau complex declines

With less inhibition of their activity, per and cry are turned on again

This cycle takes about 24 hours to complete


Peripheral clocks

The SCN may be the master biological clock But other circadian clocks throughout the body keep their

own internal time Rhythms persist in cell cultures from the SCN, liver, and

lung And in fibroblasts (generic cells) in cultures

Perhaps all cells have personal clocks


A model of circadian organization in mammals.


Clock output

The SCN entrain peripheral circadian oscillators So they are correctly set to environmental time

The phase relationship between rhythmic output of the SCN and rhythmic clock genes in peripheral tissues varies Peak clock gene expression occurs at distinct times of

the day and varies in different tissues The clock may not directly cause the rhythmic output

of peripheral tissues Most neural connections are to the hypothalamus and

autonomic nervous system, which influences hormone levels


Signals from the SCN can be neural

The SCN has at least two neural output pathways that affect rhythms One pathway goes to the preoptic nucleus of the

hypothalamus Controls the rhythm in ovulation, but not the activity

rhythm

The second pathway leads to the paraventricular nucleus in the hypothalamus

Integrates neuroendocrine and autonomic functions And then leads to the pineal, which produces

melatonin


Melatonin ( 退黑激素 )

退黑激素 (Melatonin) 有人叫聚黑激素，它是腦部「松果體」所分泌的一種激素。它可使青蛙皮膚色素細胞內之黑色素顆粒聚合於細胞核附近（故稱為聚黑激素），因而使皮膚顏色看起來較淡。

光線經過視網膜神經細胞再傳至下視丘，再經交感神經而傳至松果體，抑制退黑激素的分泌。反之，黑暗則可促使退黑激素的分泌。

下視丘內之一些細胞有如「生物時鐘」般使松果體之退黑激素分泌出現晝夜韻律之差異，一般晚上入睡後其血中濃度為白天的六倍。退黑激素在血中的半衰期甚短，約為半分鐘至５分鐘之間，主要在肝臟內代謝而其代謝物則由尿液排出。


The influence of light and darkness on circadian rhythms and related physiology and behavior through the SCN in humans


Signals from the SCN can be hormonal

Reproductive responses to the length of day and rhythms in hormones require neural connections And also small molecules that diffuse to their target

Activity rhythms are caused by the SCN’s release of chemical signals to other parts of the brain without neural connections

In mammals, the rhythmic production of two hormones (melatonin and glucocorticoids) entrain peripheral oscillators


糖皮質激素（ Glucocorticoid ）

糖皮質激素（ Glucocorticoid ），學名叫做「腎上腺皮質素」，由於可用於一般的抗生素或消炎藥所不及的病症，如 SARS 、敗血症……等，是由腎上腺皮質分泌的一類甾體激素，具有調節糖、脂肪、和蛋白質的生物合成和代謝的作用，還具有抗炎作用，稱其為「糖皮質激素」是因為其調節糖類代謝的活性最早為人們所認識。


Hormones entrain peripheral oscillators

Neural connections from the SCN cause the pineal to produce melatonin Melatonin amplifies the body temperature rhythm,

facilitates sleep, and controls photoperiodic responses Neural connections from the SCN to the anterior

hypothalamus initiate hormonal events Glucocorticoids were produced by the adrenal gland Glucocorticoids: steroid hormones that control many

physiological functions


Stop and think

Light cannot reset the clock in the SCN of people who are totally blind Consequently, their sleep-wakefulness rhythms drift out

of phase with the day-night cycle They are often sleepy during the day or wide awake at

night In one experiment, blind people were able to set their

clocks by taking a dose (10 mg) of melatonin at bedtime Why do you think this is possible?


Human circadian rhythms: jet lag

Jet lag: the most familiar way circadian clocks affect humans A syndrome of effects that includes decreased mental

alertness and increased gastric distress Caused by a disruption of circadian timing

After traveling across time zones, your biological clocks are still set to the local time of your home The clocks gradually adjust to the day-night cycle in the

new locale


Resetting biological clocks takes time

After traveling, it may take several days to reset your biological clock The more time zones crossed, the longer it takes to reset

the clock Not all body functions adjust at the same rate

Phase relationships in physiological processes are upset Your body time is out of phase with local time Your rhythms may peak at inappropriate times You suffer psychological and physiological disturbances


Stop and think

If you were traveling from Tampa Florida to San Diego California to compete in an important athletic event, what steps could you take before you left to minimize jet lag?

If you could choose the time of the event, would you choose morning or afternoon? Why?


Human circadian rhythms: human health

Nearly every physiological process in humans is rhythmic Each process peaks at the appropriate time of day

Certain acute medical conditions occur at a certain time of day

Most heart attacks and strokes occur between 6 AM and noon Blood pressure rises, platelets become stickier and

more likely to form blood clots, and the mechanism that breaks down blood clots is least active


Human circadian rhythms: human health

Asthma ( 氣喘 ) attacks mostly occur at night Levels of epinephrine (a hormone that causes the air

tubules to dilate), and cortisol (a hormone that suppresses the immune system) are low

The hormone leptin decreases appetite and ghrelin increases appetite Sleep-deprived humans have low leptin levels and

high ghelin levels, giving them a heartier appetite than usual


Circadian rhythms, sleep and energy

The clock gene is part of the circadian mechanism in mammals Clock mutant mice eat more than normal mice They gained weight, developed high cholesterol, blood

sugar and triglycerides, low insulin, and bloated fat cells


New possibilities for treating diseases

Discovering the link between the circadian clock and metabolism has opened new possibilities for treating diabetes and obesity The activity of a gene called SIRT1 is clock controlled It is modulated by how many nutrients a cell is

consuming SIRT1 responds to the energy state of a cell and

transmits that information to the clock by binding to the BMAL1-Clock complex Helping to explain why lack of sleep can increase

hunger and lead to obesity and diabetes


Summary

Clocks evolved as adaptations to environmental cycles Periods are called circadian, circalunidian, or circannual The free-running period: the period length in constant

conditions Entrainment adjusts the period length and the rhythm’s phase Daily rhythms can be entrained to light-dark and temperature

cycles Rhythmic processes match geophysical periods and are

caused by an internal biological clock Processes become rhythmic when coupled to the biological

clock


Summary

A biological clock measures time for: (1) anticipation of the environmental changes (2) synchronizing the behavior with unsensed events (3) continuous measurement of time

A functional clock enhances survival One or more master clocks (SCN) regulates other, slave clocks The master clock regulates activity through nerves and chemicals The genetic basis of circadian clocks involves feedback loops The SCN controls the pattern of gene expression in tissues The human circadian clock is related to health in several ways


問題與討論

[email protected]

Ayo 台南 NUTN 站 http://myweb.nutn.edu.tw/~hycheng/

生物時鐘 (Biological clocks) ─ 動物行為學 (Ethology) 鄭先祐 (Ayo) 國立臺南大學...

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Transcript of 生物時鐘 (Biological clocks) ─ 動物行為學 (Ethology) 鄭先祐 (Ayo) 國立臺南大學...

生物時鐘 (Biological clocks) ─ 動物行為學 (Ethology) 鄭先祐 (Ayo) 國立 臺南大學...

Documents

Transcript of 生物時鐘 (Biological clocks) ─ 動物行為學 (Ethology) 鄭先祐 (Ayo) 國立 臺南大學...

生物時鐘 (Biological clocks) ─ 動物行為學 (Ethology) 鄭先祐 (Ayo) 國立臺南大學...

Transcript of 生物時鐘 (Biological clocks) ─ 動物行為學 (Ethology) 鄭先祐 (Ayo) 國立臺南大學...