Frontier Biosciences group
Graduate School of Frontier Biosciences
Associate Professor Keiko TOMINAGAtomyk

URL: https://rd.iai.osaka-u.ac.jp/ja/d5bbﬀ3350025e27.html
The circadian clock (biological clock) is
an important system that living things
have acquired to adapt to the daily cycleof environmental changes associated with
the Earth's rotation.
In mammals, the circadian clock in the
suprachiasmatic nucleus (SCN) of thehypothalamus acts as the central clockthat generates autonomous oscillation. In
order to synchronize the internal
environmental rhythms with the externalenvironmental rhythms, the central clock
controls the appropriate phaserelationship between its own autonomous
oscillation and the periodic changes ofthe environment, and sends theinformation to the peripheral clocks
throughout the body (see the figure
below). As a result, various physiologicalphenomena such as sleep/wakefulness,
body temperature, and hormone
secretion show rhythms with peaks at
appropriate times. Light is the mostpowerful environmental factor (zeitgeber)that affects the phase and/or period of
circadian rhythms, but it is known thatenvironmental factors other than light,
such as meal timing and socialinteractions, also have effects on
circadian rhythms. We aim to clarify at themolecular level how various
environmental factors affect the circadianclock. We are also studying theaftereffects of environmental factors on
circadian rhythms, that is, the plasticity of
the circadian clock.

Mammalian circadian clock
The mammalian circadian clock islocated in the suprachiasmatic nucleus(SCN) of the hypothalamus at the bottomof the brain. The SCN is a small nucleus
with a diameter of about 300 µm on one
side. After the SCN is lesioned, allcircadian rhythms of the body disappear.
Also, the cultured SCN isolated from thebrain continue to oscillate autonomously ina cycle of about 24 hours as long as thecells are alive. Since the discovery of clock
genes, the central mechanism of theautonomous oscillation of the circadianclock has been clarified. Clock genes in theSCN are expressed with a clear andsignificant rhythm. The feedback loop oftranscription and translation of these clock
genes and their own transcriptional
regulation by their proteins is the coremechanism of the circadian clock.

Figure: Mouse behavioral rhythm in 12hr light:12hr darkcycles (LD) and constant dark conditions (DD).
The activity rhythm in DD is free running.

Various zeitgebers that affect thecircadian clock
Various environmental factors change the phaseand free-running period of the circadian clock.
Among them, light is the strongest environmental
factor that shifts the phase of circadian clock, andits effect depends on the phase (time) of thecircadian clock. We are investigating the phasedependency of effects, in which light drives thephase shift of circadian rhythms only at nighttime.
Also, when a mouse is placed under exotic lighting
conditions, the period of circadian rhythm changes
and its effect lasts for a long time as an aftereffect.
We are also interested in this kind of plasticity
phenomenon of circadian rhythm and are
conducting research on the mechanisms of thecircadian clock involved in the phenomenon. This
research is expected to lead to the elucidation of
the close relationship between our physical/mental
disorders and the malfunction of our circadianclock. We are also searching for factors other thanlight that affect the phase and period of thecircadian clock.
Circadian clocks of diurnal andnocturnal animals
Nocturnal animals such as experimental mice
(C57BL/6, BALB/c, etc.) are active at night. On
the other hand, diurnal animals such as humans
are awake during the day. Although the activity
rhythm of both is in the antiphase relationship,
the neural activity of the SCN is high in thedaytime and low in the nighttime in both diurnal
and nocturnal animals. However, it is not yet
clarified whether the properties of the circadianclock in the SCN are the same for diurnal andnocturnal. Therefore, in order to understand thehuman circadian clock, we are investigating theproperties of the circadian clock of diurnal
animals using the diurnal primate common
marmoset.
Let's unravel the mystery of
the mammalian circadian clock.

Graduate School of Frontier Biosciences,
Osaka University , 1-3 Yamadaoka, Suita, Osaka
565-0871, Japan

Figure: The SCN in culture, showing circadianrhythm after transfer to culture

TEL: +81-6-6879-4662
FAX : +81-6-6879-4661
Scan here for the lab‘s website