molecular and neural basis of circadian rhythms

• What do core clock genes generate at a single cell level?

  24 hour molecular rhythms
• What are the most important elements of the TTFL?

  BMAL1/CLOCK and PER/CRY heterodimers
• How do molecular rhythms affect neuronal activity?

  They result in changes in electrical activity
• Where is the SCN localized?

  In the hypothalamus
• What happens when the SCN is lesioned?

  Loss of behavioural rhythms occurs
• What can restore behavioural rhythmicity after SCN lesions?

  SCN explants or grafts
• What is the effect of knocking out selective core clock genes?

  Results in arrhythmic SCN and behaviour
• When is the SCN more active?

  During the light phase
• What do astrocytes rhythmically express?

  Core clock genes
• How do astrocytes affect calcium activity?

  They result in rhythmic calcium activity
• What restores behavioural rhythms in clockless mice?

  Restoring circadian rhythms in SCN astrocytes
• How do astrocytic and neuronal populations exchange information?

  Using glutamate
• What is the SCN's role in circadian rhythms?

  It is a primary circadian clock
• Where else are clock genes expressed rhythmically?

  In several brain sites and peripheral tissues
• How does the circadian clock in the choroid plexus compare to the SCN?

  It may be superior to the SCN
• What do clock genes control?

  The 24 hour loop
• What type of loop is the transcriptional-translational feedback loop?

  A secondary loop
• What activates CRY and PER when BMAL1 and CLOCK bind to E-box?

  It activates transcription
• What is the relationship between PER-CRY and CLOCK-BMAL expression?

  Close to anti-phase relation
• What do electrophysiological rhythms control?

  Transcription of ion channels
• What happens to neurons during the day?

  They become more active
• What is the primary circadian clock?

  The SCN
• What do lesions of the SCN abolish in rodents?

  Rhythms in feeding and drinking
• What can restore rhythms after SCN lesions?

  Foetal SCN graft
• What happens when CRY1 and CRY2 are deleted?

  It abolishes the SCN clock
• What is the sequence of control from molecular to behavioural?

  Molecular → electrical → behavioural
• How do normal and CRY1/2 knockout mice appear in light-dark conditions?

  Both appear behaviourally rhythmic
• How is the SCN active during the day translated into different behaviours?

  It varies across species
• What is the SCN densely populated by?

  Astrocytes
• When do astrocytes express CRY1?

  During the day
• What is sufficient for SCN timekeeping?

  The astrocytic clock
• What happens when the SCN is clockless?

  Loss of behavioural rhythmicity occurs
• What restores behavioural rhythms in astrocytes?

  Genetic manipulation
• What drives high extracellular glutamate concentrations during circadian night?

  Astrocytic release of glutamate
• What does high extracellular glutamate activate?

  Presynaptic NMDA glutamate receptors
• What does the activation of NMDA receptors facilitate?

  GABA release
• What happens during circadian daytime regarding glutamate?

  There is clearance of extracellular glutamate
• What does the clearance of glutamate relieve?

  GABAergic tone across the network
• What leads to increased electrical firing of SCN neurons?

  Relief of GABAergic tone
• What was the first idea regarding the SCN's role?

  It governs all rhythms in physiology