Forgetfulness might depend on time of day
2020-01-07 10:13

Can't remember something? Try waiting until later in the day. 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.

东京大学应用生物化学系的Satoshi Kida教授说:“我们可能是第一个在小鼠中找到记忆检索基因。”

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.

他们对健康小鼠和不含BMAL1的小鼠进行了相同的实验,BMAL1是一种调节许多其他基因表达的蛋白质。 BMAL1通常在醒来前的低水平和睡觉前的高水平之间波动。

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.

小鼠自然是夜间活动的。当使用Zeitgeber(开启光的环境提示)以时间为单位进行测量时,小鼠通常在Zeitgeber时间1到12处于睡眠状态,而在Zeitgeber时间12到24处于唤醒状态。术语“就在正常醒来之前”指的是Zeitgeber时间10 ,而术语“刚睡后”指的是Zeitgeber时间4。

Collaborators at the Tokyo University of Agriculture and the University of Toronto also contributed to this research.


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