Influence of Time of Day on Memory Recall in Mice

Circadian Clock and Its Role in Mammalian Processes

Researchers have discovered that the time of day significantly impacts memory recall, mediated by the hippocampal circadian clock in mice. The body’s internal circadian clock regulates essential mammalian functions such as metabolism, sleep patterns, heart rate, blood pressure, and body temperature. In humans, a master biological clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus coordinates secondary biological clocks, including the hippocampal clock.

Mechanism of Circadian Rhythm in Gene Expression

The circadian rhythm of gene expression is influenced by proteins BMAL1 and CLOCK, which interact to regulate gene activation based on the time of day. In nocturnal mice, BMAL1 levels are naturally lower before waking and higher before sleeping.

Recent Findings on Memory Recall

A recent study published in Nature Communications reveals that fluctuations in hippocampal BMAL1 activity play a crucial role in regulating memory recall. The researchers conducted a memory test involving two groups of mice: healthy mice and those lacking BMAL1.

Structure of the Memory Test

The memory test consisted of two phases. In the “learning” phase, mice were allowed to explore either a new juvenile mouse or a new object for a few minutes. The “recall” phase involved observing how quickly the mice recognized the same mouse or object later at different times of the day. This distinction helped researchers determine whether poor memory recall was due to ineffective learning or retrieval difficulties.

Impact of Time of Day on Memory Recall

The findings indicated that the timing of the “learning phase” did not affect memory recall in either group. However, memory recall was influenced by the time of day. Healthy mice exhibited impaired memory recall just before waking, while recall was not impaired just before bedtime. For mice without BMAL1, memory recall was consistently impaired, but those that had a longer “learning” phase showed improved recall just before bedtime but not before waking.

Conclusion and Implications

These results suggest that heightened BMAL1 activity before bedtime enhances memory recall, whereas decreased activity before waking impairs it. Further experiments revealed similar results in mice kept in constant darkness, indicating that memory recall relies on endogenous cues rather than external time indicators.

The researchers emphasize the need for future studies to confirm these findings. Although the purpose of these fluctuations in memory recall related to time of day remains unclear, they have identified connections between BMAL1 activity, dopamine receptor activation, and PKA-induced phosphorylation. Future research will aim to explore ways to modify the BMAL1 signaling pathway to improve memory recall, which could have significant implications for individuals with dementia or Alzheimer’s disease.

References

1. Hasegawa, S., Fukushima, H., Hosoda, H. et al. Hippocampal clock regulates memory retrieval via Dopamine and PKA-induced GluA1 phosphorylation. Nat Commun 10, 5766 (2019) doi:10.1038/s41467-019-13554-y
2. UTokyo_News_en. (n.d.). Forgetfulness might depend on time of day. Retrieved from https://www.eurekalert.org/pub_releases/2019-12/uot-fmd121519.php
3. Circadian Rhythms and the Brain. (n.d.). Retrieved from https://neuro.hms.harvard.edu/harvard-mahoney-neuroscience-institute/brain-newsletter/and-brain-series/circadian-rhythms-and-brain.
4. Image by Jan Vašek from Pixabay.