Case 1, Camping
Problem statement
What is the biological clock and how does it work?
Learning goals
1. What are the biological clocks and where are they located?
a. Multiple clocks: in the brain, periphery
b. SCN: SupraChiasmaticNucleus
2. What factors influence the biological clocks?
a. Light, food intake, exercise
3. What is the molecular mechanism behind the Circadian rhythm?
a. PER-protein, CRY, Clock, Bmal1
4. Which processes are regulated by the biological clock?
a. Melatonin, body temperature, heart rate
1. What are the biological clocks and where are they located?
Circadian rhythms
Circadian rhythms are near 24-hour rhythms in behavior, physiology, or metabolism. Many
cell types express the genes necessary for the transcriptional-translational feedback loop
whose molecular oscillation occurs with a ~24-hour cycle length. The suprachiasmatic nuclei
(SCN) together with many other cells and tissues have the capacity to display an
approximately 24-hour rhythmicity.
Multiple biological clocks
A biological timing system necessarily consists of an intrinsic clock mechanism that measures
time, an input mechanism that allows the clock to become synchronized or reset by changes in
the environment, and output pathways that lead to generation of overt rhythms such as daily
changes in locomotor activity, sleep, and hormone levels.
Central clock, the suprachiasmatic nuclei (SCN)
The suprachiasmatic nuclei (SCN) of the hypothalamus are unique in their role as circadian
pacemaker and play a key role in coordinating oscillations in other tissues and in regulating
behavior. These nuclei regulate behavioral and physiological rhythms, synchronizing them to
occur in the proper timing with respect to the light-dark cycle.
The primary input pathway to the SCN circadian clock is through retinal detection of light.
Remarkably, the retinal photoreceptors that lead to visual image formation are not needed for
circadian photoreception. Instead, a specialized population of retinal ganglion cells directly
detect light, project to the SCN, and are necessary for photic entrainment of the SCN clock.
The main output of the SCN is encoded in neuronal firing rates. In addition, rhythmic
neuropeptide secretion into the cerebrospinal fluid may be an important mechanism for
regulation of downstream targets. Anatomically, the outputs of the SCN are focused within
the hypothalamus but have widespread influence, consistent with the pervasive influence of
the SCN on physiological functions ranging from the modulation of cognitive function to
neuroendocrine responses. Output rhythms dependent on the SCN synchronize autonomous
oscillators in other tissues. Local circadian oscillators regulate gene expression in a tissue-
specific manner.
The SCN consists of a heterogenous population of neuronal and glial cells distributed in two
anatomic subdivision: a ventral ‘core’ region, receiving retinal input, and a dorsal ‘shell’
, region, receiving dense input from the core. A majority of core neurons express vasoactive
intestinal polypeptide (VIP), and fewer express gastrin-releasing peptide. Most shell neurons
express vasopressin. Most neuropeptides colocalize with gamma-aminobutyric acid (GABA),
and most synapses between SCN neurons are GABAergic.
Know the most important: melatonin, and vasoactive intestinal polypeptide are 2 examples
that are regulated by the SCN which in turn. VIP is really important to synch all neurons
together. Try to find a little more detail on what these do.
More details on the SCN cells itself, what is functions and what type of cells are present
Entrainment: the daily synchronization of a self-sustained
oscillator by an external signal (Zeitgeber). The most potent
synchronizes of the central clock in mammals is light
perceived by the retina.
The master clock located in the suprachiasmatic nucleus
(SCN) synchronizes a network of brain and peripheral clocks,
leading to circadian rhythms of physiologic, metabolic, and
hormonal parameters. The molecular clockwork relies on
transcriptional-translational feedback loops.
Tissues that are influenced by the day- and night-rhythm The first resource on the
resources list.
Extra-Suprachiasmatic nucleus brain clocks
Many brain regions exhibit daily oscillations of clock genes. Retina and olfactory bulbs are
the only extra-SCN brain clocks with very strong oscillatory capacities. Other brain regions,
such as arcuate nucleus and dorsomedial hypothalamic nucleus, two structures of the medio
basal hypothalamus involved in feeding and energy metabolism, are capable of self-sustained
oscillations for several cycles when isolated in vitro. Cells of these oscillators exhibit
independent circadian rhythms, but are weakly couples, and their synchronization requires
daily inputs Surprisingly, the timing of clock gene oscillations and the rhythm of electrical
activity in the secondary brain clocks differs from the SCN in most cases. Several brain
Problem statement
What is the biological clock and how does it work?
Learning goals
1. What are the biological clocks and where are they located?
a. Multiple clocks: in the brain, periphery
b. SCN: SupraChiasmaticNucleus
2. What factors influence the biological clocks?
a. Light, food intake, exercise
3. What is the molecular mechanism behind the Circadian rhythm?
a. PER-protein, CRY, Clock, Bmal1
4. Which processes are regulated by the biological clock?
a. Melatonin, body temperature, heart rate
1. What are the biological clocks and where are they located?
Circadian rhythms
Circadian rhythms are near 24-hour rhythms in behavior, physiology, or metabolism. Many
cell types express the genes necessary for the transcriptional-translational feedback loop
whose molecular oscillation occurs with a ~24-hour cycle length. The suprachiasmatic nuclei
(SCN) together with many other cells and tissues have the capacity to display an
approximately 24-hour rhythmicity.
Multiple biological clocks
A biological timing system necessarily consists of an intrinsic clock mechanism that measures
time, an input mechanism that allows the clock to become synchronized or reset by changes in
the environment, and output pathways that lead to generation of overt rhythms such as daily
changes in locomotor activity, sleep, and hormone levels.
Central clock, the suprachiasmatic nuclei (SCN)
The suprachiasmatic nuclei (SCN) of the hypothalamus are unique in their role as circadian
pacemaker and play a key role in coordinating oscillations in other tissues and in regulating
behavior. These nuclei regulate behavioral and physiological rhythms, synchronizing them to
occur in the proper timing with respect to the light-dark cycle.
The primary input pathway to the SCN circadian clock is through retinal detection of light.
Remarkably, the retinal photoreceptors that lead to visual image formation are not needed for
circadian photoreception. Instead, a specialized population of retinal ganglion cells directly
detect light, project to the SCN, and are necessary for photic entrainment of the SCN clock.
The main output of the SCN is encoded in neuronal firing rates. In addition, rhythmic
neuropeptide secretion into the cerebrospinal fluid may be an important mechanism for
regulation of downstream targets. Anatomically, the outputs of the SCN are focused within
the hypothalamus but have widespread influence, consistent with the pervasive influence of
the SCN on physiological functions ranging from the modulation of cognitive function to
neuroendocrine responses. Output rhythms dependent on the SCN synchronize autonomous
oscillators in other tissues. Local circadian oscillators regulate gene expression in a tissue-
specific manner.
The SCN consists of a heterogenous population of neuronal and glial cells distributed in two
anatomic subdivision: a ventral ‘core’ region, receiving retinal input, and a dorsal ‘shell’
, region, receiving dense input from the core. A majority of core neurons express vasoactive
intestinal polypeptide (VIP), and fewer express gastrin-releasing peptide. Most shell neurons
express vasopressin. Most neuropeptides colocalize with gamma-aminobutyric acid (GABA),
and most synapses between SCN neurons are GABAergic.
Know the most important: melatonin, and vasoactive intestinal polypeptide are 2 examples
that are regulated by the SCN which in turn. VIP is really important to synch all neurons
together. Try to find a little more detail on what these do.
More details on the SCN cells itself, what is functions and what type of cells are present
Entrainment: the daily synchronization of a self-sustained
oscillator by an external signal (Zeitgeber). The most potent
synchronizes of the central clock in mammals is light
perceived by the retina.
The master clock located in the suprachiasmatic nucleus
(SCN) synchronizes a network of brain and peripheral clocks,
leading to circadian rhythms of physiologic, metabolic, and
hormonal parameters. The molecular clockwork relies on
transcriptional-translational feedback loops.
Tissues that are influenced by the day- and night-rhythm The first resource on the
resources list.
Extra-Suprachiasmatic nucleus brain clocks
Many brain regions exhibit daily oscillations of clock genes. Retina and olfactory bulbs are
the only extra-SCN brain clocks with very strong oscillatory capacities. Other brain regions,
such as arcuate nucleus and dorsomedial hypothalamic nucleus, two structures of the medio
basal hypothalamus involved in feeding and energy metabolism, are capable of self-sustained
oscillations for several cycles when isolated in vitro. Cells of these oscillators exhibit
independent circadian rhythms, but are weakly couples, and their synchronization requires
daily inputs Surprisingly, the timing of clock gene oscillations and the rhythm of electrical
activity in the secondary brain clocks differs from the SCN in most cases. Several brain
