Forgetfulness might depend on time of day

28 Jan Forgetfulness might depend on time of day

Researchers may have identified the first gene in mice specific to memory retrieval. Many memory researchers study how new memories are made, however the biology of forgetting is more complicated to study because of the difficulties of distinguishing between not knowing and not recalling.

Researchers designed a memory test that can differentiate between not learning versus knowing but not being able to remember. They did this by testing the memories of young adult male and female mice.

In the learning, or training, phase of the memory tests, the mice were allowed to explore a new object for a few minutes. Later, in the recall phase of the test, the mice were observed for how long they touched the object when it was reintroduced. Mice spend less time touching objects that they remember seeing previously. The mice’s recall was tested by reintroducing the same object at different times of day.

Researchers 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 recognise 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 recognising 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.

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.

They now have evidence that the circadian clock is regulating memory recall through the role of BMAL1 in memory retrieval to a specific area of the brain called the hippocampus. They also connected normal BMAL1 to activation of dopamine receptors and modification of other small signalling molecules in the brain.

This is an important finding, as identifying ways to boost memory retrieval through this BMAL1 pathway may have applications to human diseases of memory deficit, like dementia and Alzheimer’s disease.


Story Source:

University of Tokyo. “Forgetfulness might depend on time of day.” ScienceDaily. ScienceDaily, 18 December 2019. <>.


Journal Reference:

Shunsuke Hasegawa, Hotaka Fukushima, Hiroshi Hosoda, Tatsurou Serita, Rie Ishikawa, Tomohiro Rokukawa, Ryouka Kawahara-Miki, Yue Zhang, Miho Ohta, Shintaro Okada, Toshiyuki Tanimizu, Sheena A. Josselyn, Paul W. Frankland, Satoshi Kida. Hippocampal clock regulates memory retrieval via Dopamine and PKA-induced GluA1 phosphorylation. Nature Communications, 2019; 10 (1) DOI: 10.1038/s41467-019-13554-y