Biological Rhythms: Circadian rhythms Aims To know the biological clock in control of the Circadian Rhythm To understand the difference between Endogeous Pacemakers and Exogenous Zeitgebers To be able to explain research into Circadian rhythms

Biorhythms A biological rhythm is any change in a biological activity that repeats periodically. Often synchronised: Daily, Monthly and annual. Circadian = 24 hour cycle; S/W cycle Infradian = 24+ hour cycle; Menstrual cycle Ultradian = <24 hours; Sleep

Biological rhythms Circadian = 24 hour cycle; S/W cycle Infradian = 24+ hour cycle; Menstrual cycle Ultradian = <24 hours; Sleep

Key concepts Biological clocks The SCN: the Master Circadian Pacemaker Clock genes – Human= CLK+BLMAL1=PER+CRY=negative feedback loop Circadian = 24 hour cycle; S/W cycle Endogenous Pacemakers regulated by Exogenous Zeitgebers Human isolation studies: Siffre Chronotherapeutics: Aspirin Individual differences: Owl/Larks Animal research ethics

The Biological Clock - How does it work? Thought mainly to be an endogenous (internal) mechanism Our internal rhythms are thought to be generated by protein synthesis within the SCN. Protein is produced for a period of hours until it reaches a level that inhibits further production. Over the next few hours the protein level gradually falls, when it drops to a certain ‘threshold’ level then production of the protein re-starts. This generates an internal (endogenous) biological rhythm – in humans of between 24 ½ and 25 hours. This is what happens inside the SCN Protein synthesis takes place over a 24 hour period

THE TICKING OF THE BIOLOGICAL CLOCK Suprachiasmatic Nucleus (SCN) The basis of the circadian rhythm lies in interactions between certain proteins, creating the ‘tick’ of the biological clock; it is an ingenious negative feedback loop. Darlington et al. (1998) first identified such proteins in the fruit fly, drospholia. In the morning, two proteins, CLOCK and CYCLE (CLK-CYC) bind together. Once joined, CLK-CYC produce two other proteins, PERIOD and TIME (PER-TIM). PER- TIM has the effect of rendering the CLK-CYC proteins inactive, so that, as PER- TIM increases, CLK-CYC decreases and therefore PER-TIM starts to decrease too (negative feedback). This loop takes about 24 hours and, hey presto, you have the biological clock! The actual proteins vary from animal to animal. In humans the main pairs are CLOCK-BMAL1 and PER-CRY (BMAL1 and CRY are also proteins). This protein mechanism is present in the SCN (the central oscillator), and is also present in cells throughout the body (peripheral oscillators). The presence of peripheral oscillators explains why there are different rhythms for different functions such as hormone secretion, urine production, blood circulation and so on.

THE TICKING OF THE BIOLOGICAL CLOCK Suprachiasmatic Nucleus (SCN) The basis of the circadian rhythm lies in interactions between certain proteins, creating the ‘tick’ of the biological clock; it is an ingenious negative feedback loop. In humans the main pairs are CLOCK-BLMAL1 and PER-CRY (BMAL1 and CRY are also proteins). This protein mechanism is present in the SCN (the central oscillator), and is also present in cells throughout the body (peripheral oscillators). The presence of peripheral oscillators explains why there are different rhythms for different functions such as hormone secretion, urine production, blood circulation and so on.

Clock genes control the proteins Clock –clock BLMAL1-BLMAL1 PER-PER CRY-CRY Proteins are produced and broken down over a 24 hour period giving us our 24 hour S/W circadian rhythm. This is called protein synthesis

Protein synthesis in the SCN: Negative feedback loop CLK PER + CRY BLMAL1 When PER and CRY bind they render CLK and BLMAL1 inactive This gives us our 24 rhythmic activity 24 hour Circadian cycle 20, 000 cells in the SCN Clock and BLMAL1 bind together to produce... Per and cry