T08 生物時鐘 (Biological clocks)

動物行為學 (通識) 國立臺南大學通識課程 2011年春 T08 生物時鐘(Biological clocks) 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/

08 生物時鐘 (Biological clocks) • 定義：Clock-controlled rhythms • Rhythmic behavior(韻律行為) • Advantages of clock-controlled behavior • Organization of circadian systems • Human implications of circadian rhythms Ayo 教材 (動物行為學 2011 通識)

定義：clock-controlled rhythms • Persistence(持續) in constant conditions • Cycles continue in the absence of environmental cues. • This means that the external day-night cycles in light or temperature are not causing the rhythms. • internal (endogenous) biological clock • Such as circadian rhythms • Entrainment(調整) by environmental cycles • To keep from getting wildly out of synchrony with the natural cycle, biological clocks need to be reset, or entrained, to the cycle. Ayo 教材 (動物行為學 2011 通識)

Animals have internal clocks(circadian rhythms) Hamsters (倉鼠), as well as all other animals, have an internal, living clock(an activity rhythm) Ayo 教材 (動物行為學 2011 通識)

Biological rhythms(生物韻律) The period (the interval between two identical points in the cycle) of the rhythm can become longer or shorter Circadian rhythm(約日韻律) ： a daily rhythm Circalunidian(約月韻律) ： a lunar day (tidal) rhythm Circamonthly(約月韻律) ： a monthly rhythm Circannual(約年韻律)：an annual rhythm Free-running period: a circadian period length under constant conditions It is not manipulated by environmental cycles Ayo 教材 (動物行為學 2011 通識)

Entrainment to environmental 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 nightresets the clock In nature, the clock is reset by light at dawn and dusk each day Ayo 教材 (動物行為學 2011 通識)

案例：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 Ayo 教材 (動物行為學 2011 通識)

Daily rhythms(circadian 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 Ayo 教材 (動物行為學 2011 通識)

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 Ayo 教材 (動物行為學 2011 通識)

案例：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 Ayo 教材 (動物行為學 2011 通識)

An activity rhythm of a fiddler crab (Uca pugnax). Althouth the crab was maintained in constant darkness and temperature(20℃). Ayo 教材 (動物行為學 2011 通識)

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 案例：In the tiny chironomid midge(蠓), emergence of adults from their pupal cases is programmed to coincide with tidal changes. Ayo 教材 (動物行為學 2011 通識)

案例：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. Ayo 教材 (動物行為學 2011 通識)

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 案例：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 Ayo 教材 (動物行為學 2011 通識)

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. Ayo 教材 (動物行為學 2011 通識)

Annual rhythms Annual biological clocks are important In timing migration(遷移) To prepare animals physiologically for migration and reproduction(生殖) 案例：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 Ayo 教材 (動物行為學 2011 通識)

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. • A constant photoperiod and variable rainfall and food abundance don’t provide proper cues to signal the time to begin migrating Ayo 教材 (動物行為學 2011 通識)

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 Ayo 教材 (動物行為學 2011 通識)

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 Ayo 教材 (動物行為學 2011 通識)

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 Ayo 教材 (動物行為學 2011 通識)

Advantages of clock-controlled behavior 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 Ayo 教材 (動物行為學 2011 通識)

1. 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 Ayo 教材 (動物行為學 2011 通識)

2. 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 Ayo 教材 (動物行為學 2011 通識)

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 Ayo 教材 (動物行為學 2011 通識)

(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. Ayo 教材 (動物行為學 2011 通識)

3. 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 Ayo 教材 (動物行為學 2011 通識)

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 Ayo 教材 (動物行為學 2011 通識)

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 Ayo 教材 (動物行為學 2011 通識)

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 Ayo 教材 (動物行為學 2011 通識)

Animals have at least one masterclock 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 Ayo 教材 (動物行為學 2011 通識)

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) Ayo 教材 (動物行為學 2011 通識)

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 retino-hypothalamic tract (RHT) A bundle of nerve fibers connecting the retina with the hypothalamus (下丘腦) 下丘腦控制體溫、飢餓、性慾、口渴、生氣、疲勞、以及生物鐘。 Ayo 教材 (動物行為學 2011 通識)

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 Ayo 教材 (動物行為學 2011 通識)

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). Ayo 教材 (動物行為學 2011 通識)

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 Ayo 教材 (動物行為學 2011 通識)

A model of circadian organization in mammals. Ayo 教材 (動物行為學 2011 通識)

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 退黑激素 and glucocorticoids糖皮質激素) entrain peripheral oscillators Ayo 教材 (動物行為學 2011 通識)

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(下丘腦)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。 Ayo 教材 (動物行為學 2011 通識)

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。 Ayo 教材 (動物行為學 2011 通識)

The influence of light and darkness on circadian rhythms and related physiology and behavior through the SCN in humans Ayo 教材 (動物行為學 2011 通識)

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 Ayo 教材 (動物行為學 2011 通識)

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 Ayo 教材 (動物行為學 2011 通識)

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 Ayo 教材 (動物行為學 2011 通識)

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 Ayo 教材 (動物行為學 2011 通識)

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(瘦體素)decreases appetite and ghrelin(食慾素) increases appetite • Sleep-deprived humans have low leptin levels and high ghelin levels, giving them a heartier appetite than usual. Ayo 教材 (動物行為學 2011 通識)

問題與討論 Japalura@hotmail.com • Ayo 台南 NUTN 站http://myweb.nutn.edu.tw/~hycheng/ Ayo 教材 (動物行為學 2011 通識)

T08 生物時鐘 (Biological clocks)