Lecture 7 When does the clock start ticking?

Question 1

newborn clocks

Answer 1

arrythmic until 3-4mo.

Question 2

old people clocks

Answer 2

weakened circadian system, nap in day, trouble sleeping at night.

Question 3

Rodent developmental ages

Answer 3

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.

Question 4

Development of visual system in rodents?

Rod/cones
mRGC

Answer 4

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

Question 5

Development of retinohypothalamic tract rodents

Answer 5

Projections to SCN start at:
Hamster - P4
Rat - P1

both fully develop by P15

Question 6

Development of SCN rodent

neurons

glia

synaptogenesis

metabolism

Answer 6

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

Question 7

Development of neuropeptides

Answer 7

neurogenesis occurs in embryo, most not expressed until after birth.

VIP expressed E13 pre birth however.

Question 8

Development of clock genes

Answer 8

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.

Question 9

development of peripheral clock genes

Answer 9

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

Question 10

Maternal clock effects on foetus

Answer 10

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

Question 11

SCN lesion effect in pregnant rat

Answer 11

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.

Question 12

effects of maternal melatonin on pups

Answer 12

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

Question 13

pinealectomy in maternal rat

Answer 13

maternal pinealectomy + melatonin replacement given at night restores syncrony to 6-12 hours.

Question 14

how is day/night cycle informed in pups wrt time spent on nest?

Answer 14

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.

Question 15

When does the SCN show light responsiveness and clock gating for:
c-fos
Per1
Per2

Answer 15

Light: c-fos at P1; Per1 at P1; at Per P3

Clock: c-fos at P10; Per1 at P3; Per2 at P5

Question 16

the transition between maternal and photic entrainment in pups?

Answer 16

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

Question 17

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:

Answer 17

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

Question 18

consequences of postnatal experience?

Answer 18

neonatal intensive care units LL.
they disturb sleep, rhythms, weight gain and visual development suffer.

create LD environments to fix.

Question 19

clock mutant mice?

LL/LD/DD during up to P21

Answer 19

LL show huge phase delay in LD.

DD free run longer than usual, 26 compared to 23.7

delayed sleep phase syndrome.

Question 20

mental health of rats with different light cycle up to P21

Answer 20

short photoperiod (8:16) rats show increased anxiety, depression (behavioural despair) and anhedonia than 16:8

Question 21

season and mental health

schiz, BD, ASD

Answer 21

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

Question 22

Postnatal photoperiod effects on the brain (anatomical)

Answer 22

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