Forgetfulness
might depend on time of day
University of Tokyo
Researchers identified a gene in mice that seems to influence memory recall at different times of day and tracked how it causes mice to be more forgetful just before they normally wake up.
"We may have
identified the first gene in mice specific to memory retrieval," said
Professor Satoshi Kida from the University of Tokyo Department of Applied
Biological Chemistry.
Every time you forget something, it could be because you didn't truly learn it -- like the name of the person you were just introduced to a minute ago; or it could be because you are not able to recall the information from where it is stored in your brain -- like the lyrics of your favorite song slipping your mind.
Many memory
researchers study how new memories are made. The biology of forgetting is more
complicated to study because of the difficulties of distinguishing between not
knowing and not recalling.
"We designed a memory test that can differentiate between not learning versus knowing but not being able to remember," said Kida.
Researchers tested the
memories of young adult male and female mice. In the "learning," or
training, phase of the memory tests, researchers allowed mice to explore a new
object for a few minutes.
Later, in the "recall" phase of the test, researchers observed how long the mice touched the object when it was reintroduced. Mice spend less time touching objects that they remember seeing previously. Researchers tested the mice's recall by reintroducing the same object at different times of day.
They did the same
experiments with healthy mice and mice without BMAL1, a protein that regulates
the expression of many other genes. BMAL1 normally fluctuates between low
levels just before waking up and high levels before going to sleep.
Mice trained just
before they normally woke up and tested just after they normally went to sleep
did recognize the object.
Mice trained at the
same time -- just before they normally woke up -- but tested 24 hours later did
not recognize the object.
Healthy mice and mice
without BMAL1 had the same pattern of results, but the mice without BMAL1 were
even more forgetful just before they normally woke up. Researchers saw the same
results when they tested mice on recognizing an object or recognizing another
mouse.
Something about the
time of day just before they normally wake up, when BMAL1 levels are normally
low, causes mice to not recall something they definitely learned and know.
According to Kida, the
memory research community has previously suspected that the body's internal, or
circadian, clock that is responsible for regulating sleep-wake cycles also
affects learning and memory formation.
"Now we have
evidence that the circadian clocks are regulating memory recall," said
Kida.
Researchers have traced
the role of BMAL1 in memory retrieval to a specific area of the brain called
the hippocampus. Additionally, researchers connected normal BMAL1 to activation
of dopamine receptors and modification of other small signaling molecules in
the brain.
"If we can
identify ways to boost memory retrieval through this BMAL1 pathway, then we can
think about applications to human diseases of memory deficit, like dementia and
Alzheimer's disease," said Kida.
However, the purpose
of having memory recall abilities that naturally fluctuate depending on the
time of day remains a mystery.
"We really want
to know what is the evolutionary benefit of having naturally impaired memory
recall at certain times of day," said Kida.
About the research
Mice are naturally
nocturnal. When measured in units of time using zeitgeber, the environmental
cue of light turning on, mice are usually asleep from Zeitgeber Time 1 to 12
and awake from Zeitgeber Time 12 to 24. The term "just before normally
waking up" refers to Zeitgeber Time 10, while the term "just after
normally going to sleep" refers to Zeitgeber Time 4.
Collaborators at the
Tokyo University of Agriculture and the University of Toronto also contributed
to this research.