Fluctuations in light intensity allow restoring the regularity of
circadian rhythms. This is the main conclusion of the work carried out
by Javier Buceta, group leader of The.Si.M.Bio.Sys. Group(Theoretical
and In Silico Modelling of Biological Systems) from the Co.S.Mo Lab
–based at the Barcelona Science Park– and Antoni Díez-Noguera, dean at
the Faculty of Pharmacy of the University of Barcelona and group leader
of Chronobiology at the Department of Physiology of the said faculty.
Ekkehard Ullner and J. García Ojalvo, from the Polytechnic University
of Catalonia (UPC) have also participated in the work.
In higher organisms, such as mammals, biological or circadian rhythms
are generated by a multicellular genetic clock which is located in two
regions of the hypothalamus that are connected to each other known as
suprachiasmatic nuclei (SCN), containing about 10,000 neurons each. In
order to generate and regulate circadian rhythms, our biological clock
needs to use the “cooperative cell behaviour” of SCN neurones.
These neurons generate self-sustained, coherent oscillations and
interact in a coupled manner –through a genetic circuit- forming a
single unique rhythm (circadian rhythm) that is very efficiently
modulated by the light-darkness alternance cycle in the 24 hours of a
Up until now, several studies had established that arrhythmia was
associated with a lack of coordination among the periodic expression of
SCN neurone proteins: in arrhythmic animals, the expression of SCN
neurone proteins is desynchronised. It was also known that constant
light is one of the triggers of arrhythmia. Neurons are only capable of
generating self-sustained and coherent oscillations (biological rhythm)
if the illumination is sufficiently low. However, when intensity is
increased, this coherent behaviour is lost and the biological rhythm is
distorted: animals become arrhythmic.
The researchers of the study looked at the possibility to restore
rhythmicity in the animals under these conditions by means of
fluctuations in light intensity and decided to use mathematical
modelling techniques to simulate the genetic and cell interactions of
the neuro-physiological system that regulates the biological clock. This
in silico experiment is of extraordinary interest because it has
enabled researchers to find out that light intensity fluctuations help
restore rhythmicity and coherence of circadian rhythms, and not the
contrary, that is, their distortion, as could be intuitively deduced.
“This research work has enabled us to explore a phenomenon known in
physics as “coherence resonance”, which shows that noise (understood as
irregular fluctuations) may be an order source. In other words, chance
is not an order that induces disorder, but totally the opposite; for
some biological processes, such as the circadian rhythm, it can be
beneficial. Noise-induced coherence has previously been established in
other systems. Our objective was to implement this coherence in the
control of circadian rhythms”, explained Javier Buceta, group leader of
In the work, researchers also worked on how interactions between
light fluctuations and intercellular coupling affected the dynamics of
the collective rhythm. The outcome of the research has helped gain
further understanding of the genetic circuit of the approximately 20,000
neurons that control circadian rhythms and, to gain further insight
into the influence exerted by the periodic expression of the involved
proteins in the synchronisation process of this multicellular clock.
“Thanks to this computer-generated simulation we have been able to
discover that light fluctuations play a constructive role by
synchronising communication -via a neurotransmitter- between neurones
The study constitutes a new example of how modelling has become a very
useful tool to discover in silico new phenomena in biological processes
that will be subsequently corroborated in vivo”, continued to explain
In support the hypothesis formulated by this in silico study, the
authors are currently conducting in vivo trials with mice. The trials
are headed by Antoni Díez-Noguera, current dean of the Faculty of
Pharmacy at the University of Barcelona, and group leader of
Chronobiology at the Department of Physiology of this faculty.
Díez-Noguera has been studying for over 30 years the structure and
functioning of the circadian rhythm in rodents.
Source : Barcelona Science Park