Tenn. – The imprinting effect, which was found in baby mice, may
help explain the fact that people born in winter months have a
higher risk of a number of neurological disorders including seasonal
affective disorder (winter depression), bipolar depression and
clocks measure the day length and change our behavior according
to the seasons. We were curious to see if light signals could
shape the development of the biological clock," said McMahon.
In the experiment,
groups of mouse pups were raised from birth to weaning in artificial
winter or summer light cycles. After they were weaned, they
were maintained in either the same cycle or the opposite cycle
for 28 days. Once they were mature, the mice were placed in
constant darkness and their activity patterns were observed.
mice showed a consistent slowing of their daily activity period,
regardless of whether they had been maintained on a winter light
cycle, or had been shifted to summer cycle after weaning. When
the scientists examined the master biological clocks in the
mouse brains, using a gene that makes the clock cells glow green
when active, they found a similar pattern: slowing of the gene
clocks in winter-born mice compared to those born on a summer
particularly striking about our results is the fact that the
imprinting affects both the animal's behavior and the cycling
of the neurons in the master biological clock in their brains,"
their experiments found that the imprinting of clock gene activity
near birth had dramatic effects on the reaction of the biological
clock to changes in season later in life. The biological clocks
and behavior of summer-born mice remain stable and aligned with
the time of dusk while that of the winter-born mice varied widely
when they were placed in a summer light cycle.
raised in the winter cycle show an exaggerated response to a
change in season that is strikingly similar to that of human
patients suffering from seasonal affective disorder," McMahon
when the imprinting occurs during the three-week period leading
up to weaning and whether the effect is temporary or permanent
are questions the scientists intend to address in future experiments.
study raises an intriguing but highly speculative possibility:
seasonal variations in the day/night cycle that individuals
experience as their brains are developing may affect their personality.
that the biological clock regulates mood in humans. If an imprinting
mechanism similar to the one that we found in mice operates
in humans, then it could not only have an effect on a number
of behavioral disorders but also have a more general effect
on personality," said McMahon.
to emphasize that, even though this sounds a bit like astrology,
it is not: it's seasonal biology!" McMahon added.
this study were raised on artificial seasonal light cycles in
the laboratory and the study was repeated at different times
of the year. In humans, studies conducted in the northern and
southern hemispheres have confirmed that it's the season of
winter – not the birth month – that leads to increased risk
of schizophrenia. There are many possible seasonal signals that
could affect brain development, including exposure to flu virus.
This study shows that seasonal light cycles can affect the development
of a specific brain function.
from previous studies that light can affect the development
of other parts of the brain, for example the visual system.
Our work shows that this is also true for the biological clock,"
was performed with a special strain of genetically engineered
mice that it took McMahon two years to develop. The mice have
an extra gene inserted in their genome that produces a naturally
fluorescent green protein causing the biological clock neurons
in their brains to glow green when they are active. This allows
the scientists to directly monitor the activity of the master
biological clock, which is located in the middle of the brain
behind the eyes in a small area called the suprachiasmatic nucleus
study, the researchers took three groups of six to eight newborn
pups each and placed them (and their mothers) in environments
with controlled day/night cycles. One group was placed in a
"summer" cycle with 16 hours of light and eight hours of dark;
another group was placed in a "winter" cycle with eight hours
of light and 16 hours of dark; and a third group was placed
in an equinox cycle with 12 hours of light and 12 hours of darkness.
They were kept in these environments for three weeks until they
are born, the brains of mice are less developed than those of
a human baby. As a result, their brains are still being wired
during this period," McMahon said.
were weaned, half of the summer-born mice were kept on the summer
cycle and half were switched to the winter cycle for the following
28 days as they matured. The winter-born mice were given the
same treatment. The equinox-born mice were split into three
groups and put into summer, winter and equinox cycles.
mice matured, they were placed into an environment of continuous
darkness. This eliminated the day/night cues that normally reset
biological clocks and allowed the scientists to determine their
biological clock's intrinsic cycles.
found a substantial difference between the summer-born and winter-born
mice behaved the same whether they had been kept on the summer
cycle or switched to the winter cycle. They started running
at the time of dusk (as determined by their former day/night
cycle), continued for ten hours and then rested for 14 hours.
of the winter-born mice was much different. Those who had been
kept on the winter light cycle through maturation showed basically
the same pattern as their summer cousins: They became active
at the time of dusk and continued for 10 hours before resting.
However, those who had been switched to a summer cycle remained
active for an extra hour and a half.
looked at what was happening in the brains of the different
groups, they found a strikingly similar pattern.
In the summer-born
mice, the activity of the neurons in the SCN peaked at the time
of dusk and continued for 10 hours. When the winter-born mice
were matured in the winter cycle, their neuronal activity peaked
one hour after the time of dusk and continued for 10 hours.
But, in the winter-born mice switched to a summer cycle, the
master bioclock's activity peaked two hours before the time
of dusk and continued for 12 hours.
looked at the equinox group, the scientists found variations
that fell midway between the summer and winter groups. Those
subjected to a summer cycle when they matured had biological
clocks that peaked one hour before the time of dusk and the
biological clocks of those subjected to a winter cycle peaked
a half hour after the time of dusk. In both cases the duration
of SCN activity was 11 hours.
showed that these variations are caused by alterations in the
activity patterns of the individual neurons, rather than by
"It is quite
striking how closely the neuronal wave form and period line
up with their behavior," McMahon said.
completed his graduate studies and is now assistant director
of the Vanderbilt Brain Institute. The undergraduate contributors
to the study were John Axley and Benjamin Strauss, who have
graduated and gone onto graduate school and medical school.
Karen Gamble, the contributing post-doctoral fellow, is now
a faculty member in the psychiatry department at the University
of Alabama Birmingham.
was funded by grants from the National Institutes of Health
and was conducted in association with the Silvio O. Conte Neuroscience
Research Center at Vanderbilt.
David Salisbury, (615) 322-NEWS