Lecture 1 – internal biological clock
Rhythms:
- Tidal: 12 hours
- Circadian: 24 hours
- Circatrignitan: 30 days
- Circannual: 12 months
Advantages of having a (circadian) rhythm/clock:
- Anticipation of predictable things in external conditions (light, temperature,
water, food, etc.) and adapt activities to this.
- Efficient use of sources: produce offspring when circumstances are optimal, only
when food is available (mostly for animals)
- Temporal segregation of incompatible processes, e.g. hibernation, to have better
chance of survival
These mechanisms contribute to homeostasis but they are predictive. In the genes there
is a clock which tells the body the time and can predict.
First clock found by Jean d’Ortous deMairam in 1729 by looking at opening and closing of
leaves of the Mimosa tree.
,Free running rhythm: when there is no time clue, you are going to follow the rhythm of
your endogenous biological clock. Example of free running rhythm:
In 20 days the rhythm changed 24 hours (thus animal lived a day longer than it thought it
did). The free running rhythm in this animal is 25.2 hours. (20*24)/19 = 25.3
When humans are put in darkness their rhythm also changes, often to a rhythm of more
than 25 hours.
,Fase advance: he starts running earlier every day. In 14 days there is a 7 hours phase
advance. This is 0,5h/external day thus the free running rhythm takes 23.5 hours.
Light is zeitgeber, it enters the eyes and travels through the lateral geniculate nucleus for
vision and the suprachiasmatic nucleus responsible for the biological clock. Light
enters and there are specialized ganglions which have a photopigment called
melanopsin. Then a signal travels via Retinohypothalamic tract (nerve fiber from retina
to hypothalamus). Usually Glutamate is the neurotransmitter (excitatory amino acid) or
PACAP (peptide with cAMP activating activity). Vasopressin is a neurotransmitter in the
brain which is quite abundant in the SCN.
When the sun is up, there is a lot of glutamate released and then the SCN is really active.
When the sun is down, it is inactive.
, The pineal gland/epiphysis makes melatonin
Light -> SCN -> hypothalamus -> intermediate lateral cell column (part of sympathetic
nervous system) -> it shuns somewhere and comes back -> upper superior cervical
ganglion -> pineal gland -> melatonin released into blood -> melatonin feeds back to the
whole body but especially the SCN
In more detail:
1. Light comes in 460-480 nm (blueish light) and stimulates melanopsin
2. Retinohypothalamic tract releases PACAP and glutamate
3. PACAP and glutamate travel through their receptors (NMDA for glutamate)
4. As a reaction on this:
a. PACAP -> cAMP goes up
b. Glutamate -> Ca2+ goes up
5. Clock genes are activated
6. The SCN releases neurotransmitters (GABA/vasopressin)
7. This inhibits the paraventricular nucleus (hypothalamus) (during day, PVN is
inhibited)
The SCN is stimulated by light during the day and starts to make genes. These genes are
under control of transcription factors, so it starts producing clock genes. These clock
genes produce clock proteins that feedback to the transcription factors (feedback).
During night:
PVN can stimulate the cell column -> superior cervical ganglion -> noradrenaline is
released -> binds to beta-1 receptor -> stimulates cAMP -> pineal gland starts to
produce melatonin.
Rhythms:
- Tidal: 12 hours
- Circadian: 24 hours
- Circatrignitan: 30 days
- Circannual: 12 months
Advantages of having a (circadian) rhythm/clock:
- Anticipation of predictable things in external conditions (light, temperature,
water, food, etc.) and adapt activities to this.
- Efficient use of sources: produce offspring when circumstances are optimal, only
when food is available (mostly for animals)
- Temporal segregation of incompatible processes, e.g. hibernation, to have better
chance of survival
These mechanisms contribute to homeostasis but they are predictive. In the genes there
is a clock which tells the body the time and can predict.
First clock found by Jean d’Ortous deMairam in 1729 by looking at opening and closing of
leaves of the Mimosa tree.
,Free running rhythm: when there is no time clue, you are going to follow the rhythm of
your endogenous biological clock. Example of free running rhythm:
In 20 days the rhythm changed 24 hours (thus animal lived a day longer than it thought it
did). The free running rhythm in this animal is 25.2 hours. (20*24)/19 = 25.3
When humans are put in darkness their rhythm also changes, often to a rhythm of more
than 25 hours.
,Fase advance: he starts running earlier every day. In 14 days there is a 7 hours phase
advance. This is 0,5h/external day thus the free running rhythm takes 23.5 hours.
Light is zeitgeber, it enters the eyes and travels through the lateral geniculate nucleus for
vision and the suprachiasmatic nucleus responsible for the biological clock. Light
enters and there are specialized ganglions which have a photopigment called
melanopsin. Then a signal travels via Retinohypothalamic tract (nerve fiber from retina
to hypothalamus). Usually Glutamate is the neurotransmitter (excitatory amino acid) or
PACAP (peptide with cAMP activating activity). Vasopressin is a neurotransmitter in the
brain which is quite abundant in the SCN.
When the sun is up, there is a lot of glutamate released and then the SCN is really active.
When the sun is down, it is inactive.
, The pineal gland/epiphysis makes melatonin
Light -> SCN -> hypothalamus -> intermediate lateral cell column (part of sympathetic
nervous system) -> it shuns somewhere and comes back -> upper superior cervical
ganglion -> pineal gland -> melatonin released into blood -> melatonin feeds back to the
whole body but especially the SCN
In more detail:
1. Light comes in 460-480 nm (blueish light) and stimulates melanopsin
2. Retinohypothalamic tract releases PACAP and glutamate
3. PACAP and glutamate travel through their receptors (NMDA for glutamate)
4. As a reaction on this:
a. PACAP -> cAMP goes up
b. Glutamate -> Ca2+ goes up
5. Clock genes are activated
6. The SCN releases neurotransmitters (GABA/vasopressin)
7. This inhibits the paraventricular nucleus (hypothalamus) (during day, PVN is
inhibited)
The SCN is stimulated by light during the day and starts to make genes. These genes are
under control of transcription factors, so it starts producing clock genes. These clock
genes produce clock proteins that feedback to the transcription factors (feedback).
During night:
PVN can stimulate the cell column -> superior cervical ganglion -> noradrenaline is
released -> binds to beta-1 receptor -> stimulates cAMP -> pineal gland starts to
produce melatonin.
