Circadian Rhythm Flashcards
circadian rhythm
biological rhythm with a 24hr period that persists in constant conditions
present in all organisms
benefit of the CR
survival advantage because organisms can anticipate rather than respond to environmental changes
CR functions
anticipates regular changes in the environment - tunes internal physiology to the external world
internal synchronisation (temporal organisation) - internal processes in different organs are coordinated
allow synchrony (temporal organisation) between species
examples of CRs
behavioural - sleep/wake, drinking, food
biological - glucose uptake, metabolic rate, alcohol degradation
physiological - bp, HR, pain threshold
amplitude
measures robustness of circadian period (highest to lowest period)
period
duration of one complete cycle in rhythmic variation
free running (tau)
rhythm free runs according to circadian clock H>24hrs mouse<24hrs
constant conditions, no external cues
entrainment
synchronisation of internal biological rhythms by external cues
zeitgeber
external cue
light is the primary zeitgeber
e.g. food intake/temperature
actogram
graph in CR research
vertical line = activity
exogenous vs endogenous daily rhythms
exogenous - response to change in environment by external/environmental rhythms (not internally generated)
endogenous - generated internally within the organism by a self-sustaining oscillator/biological clock (true CR)
what is the endogenous master clock
suprachiasmatic nucleus (SCN)
located at base of hypothalamus (above optic chiasm)
light perception
light detected by retina
impulses sent to SCN to entrain clock
rod and cones send signal to RGC via bipolar cells
how do RGCs detect light
melanopsin (opsin photopigment)
found in intrisically photosensitive RGCs (ipRGCs)
endoded by Opn4 gene
roles of melanopsin
light modulation of sleep
entrainment of CR
pupillary light reflex
exacerbates migraines
3 SCN inputs
1)input light pathway: retina-SCN via RHT
2)intergeniculate leaflet (IGL) innervation IGL-SCN conveys photic and non-photic info from dorsal raphe nucleus
3)DRN activated and MRN mediate entraining of arousal (non-photic)
role of CLOCK/BMAL1 heterodimers
produce Cry1/Cry2/Per1/Per2 genes in early circadian days - inhibited by nuclear accumulation of Per/Cry complex (late circadian days)
oscillatory feedback loop
core controlled genes (CCGs)
24 hrs to transcribe/translate genes - next cycle when Per/Cry degrades
rev-erb + per&cry
TF/represses Bmal1
negative regulator of Bmal1 (anti-phase to Per/cry) enhances core oscillations
mPer1 gene expression
highest expression during the mid circadian day (low proteins levels)
low mPer1 mRNA at the end of the circadian day (highest protein levels)
mPer1 mRNA expression occurs only when nuclear mPer1 protein cleared at the end of the circadian night
light entraining
RHT releases glutamate & PACAP
increases Ca2+ in SCN
activates MAPK/CaMK/PKA
CREB phosphorylation
Per regulation light resets cycle by increasing Per1/Per2 (clock genes)
hamster CR
> 24hrs
Tau mutant hamster has a shorter CR
Tau encodes protein kinase which phosphorylates Per1 and controls entry into nucleus
Casein Kinase I epsilon - degrades Per1/PTM of cry/per/changes length of TTFL/controls ability to go back to nucleus
in vitro CR monitoring
obtain single SCN neurons expressing bio-luminescence reporter gene per-1 luciferase
measure: individual cell oscillations and population
individuals SCN neurons retain CR activity and different period lengths (light up at different time) - cell-cell communication is important
structure of SCN neurons
shell: AVP/GABA
core: GRP/GABA/VIP
axon projects from core to shell, GABA is an activator and acts on shell, core synchronises shell, shell generates most SCN output, VIP excitatory action (binds VPAC2) like PACAP
VIP KO mice
Welsh et al., 2010
decreased transcription of per
desynchronised firing of SCN
weak behavioural rhythms