Lecture 7 When does the clock start ticking? Flashcards
newborn clocks
arrythmic until 3-4mo.
old people clocks
weakened circadian system, nap in day, trouble sleeping at night.
Rodent developmental ages
E0 - moating conception followed by 21 day pregnancy.
P0/E21 - birth
P21 - lactation period/weaning, seperates from mother.
5-9 weeks later reach sexual maturity.
Development of visual system in rodents?
Rod/cones
mRGC
Rod/cones maturation:
E15-P10.
Rod/cone photosensitivty maturation:
P10-P15
mRGC maturation:
E15-P0
mRGC photosensitivity maturation:
P0-P10
Overall functional retinal output:
P3-P15 roughly.
eye opens P15
Development of retinohypothalamic tract rodents
Projections to SCN start at:
Hamster - P4
Rat - P1
both fully develop by P15
Development of SCN rodent
neurons
glia
synaptogenesis
metabolism
SCN neurons begin formation in embryo:
E15-E18
SCN glial cell formation:
E15-P10 but most appear first week after birth.
synaptogenesis:
connections within SCN between neurons, also of SCN to other areas.
Just before birth ~E18 - P10
SCN metabolism:
measure using glucose.
just before birth ~E18 - P10.
SCN is therefore fully developed by P10
Development of neuropeptides
neurogenesis occurs in embryo, most not expressed until after birth.
VIP expressed E13 pre birth however.
Development of clock genes
a newborn rat P1:
low amplitude arrthymic expression of Per1/2 Cry1 Bmal1
From P2 Per1/2 have rhythm.
by P10 all above have same as adult rat.
development of peripheral clock genes
use Per1-luc to measure bioluminescence.
SCN first place to show expression - P7
Pineal gland - P9
Adrenal gland and lungs - P10
Thyroid - P20
Liver - P25
Maternal clock effects on foetus
melatonin secreted from the pineal gland, can cross placenta and sync the SCN of feotus.
key sync of foetal clock pre birth.
(possible signalling from periph clocks across placenta to foetus periph clocks)
rhythms from above at birth are lost, recovered once SCN is fully developed
SCN lesion effect in pregnant rat
Arrythmic locomotor activity; show circadian rhytm but there is litter asynchrony; each set to a different start point and so are not synced to each other.
effects of maternal melatonin on pups
maternal melatonin entrains rhythm of drinking behaviour in rat pups, melatonin has a role in sync foetal SCN.
also helps inform day/night rhythms in humans
pinealectomy in maternal rat
maternal pinealectomy + melatonin replacement given at night restores syncrony to 6-12 hours.
how is day/night cycle informed in pups wrt time spent on nest?
while mother in thenest, pups can feed, are warm.
leaves nest in nighttime.
as time progresses, spend less time in nest, and number of pups leaving the nest increases.
When does the SCN show light responsiveness and clock gating for:
c-fos
Per1
Per2
Light: c-fos at P1; Per1 at P1; at Per P3
Clock: c-fos at P10; Per1 at P3; Per2 at P5
the transition between maternal and photic entrainment in pups?
P0-P10 SCN of pup is developing, so can’t sync to light properly, depends on mother heavily.
P10-P21 depend more on environment, but still mother
P21 during weaning, don’t depend on mother,
SCN fully developed P10
extreme light environments
PO - P21
Either DD, LD or LL
followed by LD P21 - P50
PER2::LUC in SCN.
Locomotor activity:
photoreceptor response:
conclusions of the timing of the effect of the postnatal environment during lactation in rats:
PER2::LUC in SCN.
reduced amplitude for DD
lactation?
PER2::LUC rhythms in peripheral tissues of adults are affected by postnatal light environment.
reduced amplitude for heart in DD.
lung increase amp DD.
spleen no change.
liver normal as food the zeitgeber not light.
Locomotor activity:
all free run, but LL free running period reduced, increased in DD.
photoreceptor response:
a-wave (rod/cones)
b-wave (bipolar cells)
no difference for DD/LD/LL
no difference in pupillary light reflex either.
therefore light environment 3 weeks after birth doesn’t affect retinal function, but does effect SCN, peripheral clocks and behavioural/circadian output
consequences of postnatal experience?
neonatal intensive care units LL.
they disturb sleep, rhythms, weight gain and visual development suffer.
create LD environments to fix.
clock mutant mice?
LL/LD/DD during up to P21
LL show huge phase delay in LD.
DD free run longer than usual, 26 compared to 23.7
delayed sleep phase syndrome.
mental health of rats with different light cycle up to P21
short photoperiod (8:16) rats show increased anxiety, depression (behavioural despair) and anhedonia than 16:8
season and mental health
schiz, BD, ASD
generally winter babies more at risk for mental health disorders
100 studies show schizophrenia more common Dec-Feb births
10 studies show BD more common in Jan-Apr births
10 studies show ASD more common in Mar-Aug births
Postnatal photoperiod effects on the brain (anatomical)
Generally summer brains are heavier than winter brains
Males: superior temporal gyrus different
Females:
Temporal lobe - Middle temporal gyrus - Fusiform gyrus Prefrontal cortex - Posterior cingulate - Cerebellum inferior - Superior parietal lobule
impact of early life on brain development
