Circadian rhythms and sleep Flashcards
Circadian clock
Endogenous molecular pacemaker
Daily oscillations
Core molecular clock
subset of evolutionarily conserved genes that drive oscillations
Free run
biological rhythm exists without external input or cues.
Entrainment
Biological rhythm synchronised to external (light/dark) oscillation
Allows adaptation to different lengths of day (seasons)
Period clock mutants
per0 mutant alleles produce arrhythmicity
PerL produced long period rhythms
PerS produced short period rhythms
Circadian rhythm properties
Oscillations persist under constant conditions
Events recur approximately every 24 hours
Rhythms entrained by changes in light and temperature
Period of clock is stable over a wide temperature range
Parts of the circadian system
Core clock keeps time
Input pathways synchronise clock to environment
Output pathways transmit information to organise behaviour
Core clock negative feedback loop
Clock/Cycle protein complex binds E-box in promotor of period and timeless genes
PER and TIM proteins modified by doubletime and phosphatases
PER/TIM dimerise, move to nucleus and repress CLK/CYC
Can bind SLIMB(E3) for proteolysis
Zeitgebers
Harmonise clock neurons to the environment
Light, temperature, social cues
Light
Reaches clock neurons via rhodopsin-containing photoreceptive organs
Activates crytptochrome. Cry recruits Jetlag which ubiquitinates Tim for degradation
Jet ubiquitinates Cry in absence of Tim
PDF neurons
Output transmitter of clock
act as internal zeitgeber
Phase neuron oscillations to right time of day
Light-input and arousal factor of clock
Morning activity
Promoted by s-LNvs and DN1s
Evening activity
Promoted by LNds and fifth PDF-negative s-LNv
DN1s but very weak in high light
Sleep regulation
Circadian regulation is timing of sleep (preferred bedtime)
Homeostatic increases drive to sleep the more time spent awake
SLEEPLESS
Identified via forward genetic screen
Required for sleep in Drosophila
Signalling molecule that connects sleep drive to lowered membrane excitability
Loss leads to 80% reduction in sleep