Circadian clocks: how rhythms structure life

Martha Merrow, Till Roenneberg

Ludwig-Maximilians-Universität München (LMU)

Lecture 1: Introduction to chronobiology

Lecture 2: Circadian formalisms and entrainment

Lecture 3: Molecular mechanisms

Lecture 4: What does the circadian clock regulate: the concept of "clock control"

Lecture 5: Human circadian clocks in real life

Lecture 6: Pathologies and the clock

Lecture 1: Introduction to chronobiology
Rhythmic structure of life, ecology from chronobiologist perspective, temporal structure of environment and chronotopes, biological circa-rhythms and characteristics, circa-rhythms synchronise (entrain), suprachiasmatic Nuclei (SCN) as central circadian pacemakers, circadian rhythm in animals, plants, fungi and cyanobacteria, circadian clock properties like self-sustainment in constant conditions, entrainment to zeitgebers and temperature compensation, chronobiological terms and graphs

1.0 Introduction to the First Half of Lecture 1
  • Biological rhythms come in many different periods ranging from ms to years
  • Developed to help organisms cope with environmentals physical rhythms

1.1 The Family of Biological Rhythms

  • Short rhythms are typical for neuronal networks that process information, with the help of oscillations
  • Population rhythms are generated by predator and prey
    • Tracked fur trade
  • Lags between different active components of an oscillation is important
  • Heart rate and breathing frequency correlate with animal size and metabolic speed
  • Sleep cycles at non-REM to REM at ~ 90 min.
  • Biological rhythms
    • SCN processes
    • Respiration heart rate
    • REM+non
    • Circa-Tidal (bottom 4 are temporal)
    • Circa-Dian
    • Circa-Lunar
    • Circa-Annual
  • Main four
    • Tidal
    • Circadian
    • Lunar
    • Annual
    • Allow organisms to exploit temporal niches
      • Dark/light
      • Cold/warm
      • Wet/dry
  • Our internal eye (endogenous internal image), immediate spatial environment is self-sustained
    • Same for temporal structures
1.2 The Circa-Rhythms
  • Biological function that responds to light needs constant external information
    • Complex light responses may have delayed onset/tapered offset
  • Self-sustained rhythms continue without external info
    • Because periods in constant conditions may deviate from original cycle length
      • Called Circa-rhythms
  • Day length is photoperiod
  • Even human birth rates reflect seasonal differences in successful conceptions
    • Correlating with photoperiod and ambient temperatures
1.3 Spatial and Temporal Niches
  • Spatial is biotope
  • Temporal is chronotope
1.4 The Case of Gonyaulax polyedra
  • Chronobiology of single cell organism
    • Create gas bubbles and float, then photosynthesis during day
    • Sink and gather nutrients and bioluminate at night
      • And glow to stay together
1.5 Introduction to the Second Half of Lecture 1
  • Daily rhythms may be a property to all life. Major functions and behaviours are clock regulated
  • Second half is clocks in animals, plants, fungi and bacteria
1.6 Circadian Rhythms in Mammals
  • All have rhythms based on temp, sunlight, hormones (melatonin)
  • Measured rhythms in isolation chambers and with mice
1.7 Circadian Clocks in Flies, Plants and Fungi
  • Suprachiasmatic nucleus SCN is the cercadian pacemaker, dictating sleep-wake behaviour
  • Rhythm is based on each cells action
  • Sunflower changes orientation in day, some plants flower at specific times
  • Common properties of clocks: free running period, entrainment with zeitgebers, temperature compensation
  • Temperature compensation in biological systems, circadian systems act more like a clock instead of a thermometor
1.8 Wrap up for Lecture 1
  • Visualize circadian rhythms via a double plot to capture many parameters at once
  • Period - time after which a definite phase of oscillation reoccurs
  • Frequency - reciprocal of period, 1/(over) period
  • Zeitgeber (time giver) - forcing osscillations that entrain a biological rhythm
  • Tau - period of biological rhythm
  • Large T - period of Zeitgeber
  • Alpha - activity time 
  • Rho (looks like p) - rest time 
  • LD (light-dark cycle), LL (continuous illumination), DD (continuous darkness), ex LD 12(L):12(D)
  • Circadian time - time scale covering one full circadian period divided into a circadian day (24 hrs)
  • Zeitgeber time - time scale covering a 24 hours usually a 12:12 cycle