When does the clock start ticking?
BIOL31681 Clocks, Sleep & the Rhythms of Life
Dr. Maria Canal
To be covered in this lecture
1. Circadian system development
2. Maternal effects
3. Effects of environmental light
1. General development
Human developmental ages
1. General development
Rodent developmental ages
Sexual maturity
Oestrus
Weaning
P21
Birth
P0/E21
E – Embryonic day
P – Postnatal day
Mating
Conception
Gestation
E0
The mammalian circadian system
Eyes
Behavioural /
physiological
rhythms
SCN
Brain
Peripheral
clocks
2. Development of the circadian
system
Visual system
Lactation
Foetus
Birth
E15
P0
Weaning
P10
P15
P21
Rod and cone maturation
Rod and cone photosensitivity maturation
mRGCs maturation
mRGCs photosensitivity maturation
Functional retinal output
Eye opening
Adult
2. Development of the circadian
system
Retinohypothalamic tract
E21/22
P15
2. Development of the circadian
system
Suprachiasmatic nucleus
Lactation
Foetus
Birth
E15
P0
Weaning
P10
SCN neuron formation
SCN glia formation
Synaptogenesis
SCN metabolism
P15
P21
Adult
3. Development of circadian rhythms
Neuropeptides
Neurogenesis
Neuropeptide expression
3. Development of circadian rhythms
Clock genes
Per1
Per2
Rat, mRNA
Cry1
Bmal1
Sumová et al., 2009
Peripheral clock gene development
Lactation
Foetus
Birth
E15
P0
Adult
Weaning
P10
P15
P21
P7, SCN
P9, Pineal
Relative bioluminescence (%)
P10, Adrenal
Per1-luc
P10, Lungs
P20, Thyroid
P25, Liver
Days
Yamazaki et al., 2009
4. Maternal effects
Mother
Foetus
Eyes
Pineal
gland
SCN
Peripheral
clocks
P
l
a
c
e
n
t
a
Melatonin
SCN
?
?
Peripheral
clocks
4. Maternal effects
Suprachiasmatic nucleus
SCN-lesioned
animals become
arrhythmic
4. Maternal effects
Suprachiasmatic nucleus
Pups of arrhythmic mothers
develop circadian rhythms
…but there is litter asynchrony!
4. Maternal effects
Entrainment by melatonin
Bellavía et al., 2006
4. Maternal effects
Entrainment by maternal hormones
Maternal
hormones
with a diurnal
pattern are
strong
candidates for
entraining the
foetal
circadian
rhythm
Bates and Herzog, 2020
4. Maternal effects
Maternal behaviour
Mother spends progressively less
time on nest while…
… number of pups out of the nest
progressively increases
5. Effects of environmental light
Development of light sensitivity
SCN
Light pulse
Shell
Core
Eye
c-fos
Per1
Per2
Light responsiveness
P1
P1
P3
Clock gating
P10
P3
P5
Maternal vs. photic entrainment
E15
P0
P10
P15
P21
Photoperiodism
Per1::GFP in SCN
P0
P21
P50
8:16h
12:12h
16:8h
Persistent effects of perinatal
seasonal photoperiod on SCN
rhythms
Ciarleglio et al., 2011
Extreme light environments
P0
P21
P50
Dark onset advanced 8h every 2 days
Ameen et al., 2022
Neurons from disrupted group showed
significantly reduced branching and
dendritic length
Disrupted postnatal light environments have long-term
effects on neuron morphology
Postnatal light effects
Eyes
Health consequences?
- Stress
- Sleep
- Mental health
SCN
Brain
Peripheral
clocks
Behavioural /
physiological
rhythms
6. Consequences of postnatal experience
Neonatal Intensive Care Units
 Disturbances biological rhythms
 Disturbances sleep states
 Effects on postnatal weight gain
 Effects on visual development
6. Consequences of postnatal experience
Long-term effects on sleep – mice
Clock-mutant mice
P0
P21
P50
DD
LD
LL
Delayed Sleep
Phase
Syndrome
Wakatsuki et al., 2007
6. Consequences of postnatal experience
Long-term effects on sleep – humans
People born under long
photoperiods (MarchSeptember) have an earlier
chronotype
Didikoglu et al., 2019
6. Consequences of postnatal experience
Long-term effects on mental health
P0
P21
P50
8:16h
16:8h
Depression- and anxiety-like
behaviours differ between mice
raised under short, winter-like
photoperiods vs. long, summerlike photoperiods
Anxiety
Depression
Ciarleglio et al., 2011
6. Consequences of postnatal experience
Long-term effects on behaviour
P0
P21
P50
Mice from disrupted group showed:
 increased anxiety-like behaviour
 poorer spatial memory
 impaired working memory
Disrupted postnatal light environments have long-term
effects on animal behaviour
Ameen et al., 2022
6. Consequences of postnatal experience
Long-term effects on mental health
Season of birth may play a pathogenic role in the development of
mental disorders
Castrogiovanni et al., 1998
6. Consequences of postnatal experience
Long-term effects on the brain
Males:
- Superior temporal gyrus
Females:
- Temporal lobe
- Middle temporal gyrus
- Fusiform gyrus
- Prefrontal cortex
- Posterior cingulate
- Cerebellum inferior
- Superior parietal
lobule
Pantazatos, 2014
Early life programming
Fetal, neonatal and postnatal
environment (diet, stress, light)
Development
Genetic background
 Circuit formation
 Neuronal activity
 Gene expression
-
Cardiovascular disease
Obesity
Hypertension
Responses to stress
Mental health
Circadian rhythm alteration
Adolescence/adulthood