How does circadian rhythm disruption affect memory?

(Photo provided by Incé Husain)

“I hope that the results of this study make people reflect on how important it is to maintain routines that align with their daytimes and nighttimes. Even a short span of misalignment could alter how we learn and maintain memory.” ~Incé Husain

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*In the following article, TS refers to The Synapse and IH refers to Incé Husain

TS: Could you briefly introduce yourself, your supervisor, the topic of your thesis, and the field it contributes to?

IH: I’m Incé Husain, and I completed my Honours in Psychology with a Specialization in Neuroscience in April 2023. I worked with Dr. Scott Deibel on a neuroscience project that looked at the dynamics between circadian rhythms and memory. This project contributes generally to the field of circadian rhythms research, but more specifically to studying memory in the context of circadian rhythms; this has become a popular research focus in recent years.

TS: What was the inspiration for your study, your research question, the methods of the study, and the main results?

My study was inspired by past literature that sought to understand how circadian rhythm disruption affects memory. I’ll start with a general intro into circadian rhythms and provide some context into where this past literature came from.

In simple terms, circadian rhythms refer to any biological cycle that fluctuates on a 24-hour span and is regulated by a brain region called the suprachiasmatic nucleus. The most familiar examples of circadian rhythms are sleep cycles, but other intuitive examples are body temperature (our temperature rises in the day and dips at night), or diet (we get hungry at specific times of day). The goal of circadian rhythms is to ensure that we are well-synchronized with our environment. Our circadian rhythms can shift to accommodate changing environments - such as changes in light, temperature, or social interaction. This ‘shifting’ is called ‘entrainment’, and familiar examples include adapting our cycles to new time zones, night shifts, or seasonal changes.

Though entertainment serves to help us thrive in new environments, it has its limits. Entrainment becomes difficult in conditions where we don’t give our rhythms enough time to adjust to new environments, or we maintain routines that are counter to our environment. These are conditions that cause ‘circadian disruption’. In our modern-day society, circadian disruption is prevalent, and all of us can likely relate to this! Some examples of circadian disruption include maintaining work routines that involve nighttime wakefulness; traveling frequently across time zones; or overexposing ourselves to artificial (cellphone) light at night. These conditions make it difficult for our circadian rhythms to adjust render our circadian rhythms unable to entrain, and so they become misaligned with our environment. Given the prevalence of circadian disruption, current research in circadian rhythms seeks to identify the consequences of circadian disruption on cognition. A major area of current research is on how circadian disruption affects memory.

Past findings on circadian rhythms and memory have been inconsistent. Some studies mostly done in rats - show that circadian misalignment triggers deficits in memory, whereas others show that memory persists. My thesis tried to address this inconsistency by studying the relationship between circadian disruption and memory from a genetic perspective. Specifically, I analyzed how gene expression in the rat hippocampus - the area of the brain associated with memory - changes in response to circadian misalignment. Gene expression is how our bodies make proteins.

My study involved analyzing a pre-collected dataset of hippocampal gene expression in rats that had normal circadian rhythms and rats that had experimentally undergone circadian disruption through exposure to light conditions that they were unable to adjust to. Collectively, this gene expression dataset had data for over 60 000 genes in it! I would have loved to analyze every single one, but in the interest of my thesis deadline I chose eighteen genes that were discussed in past circadian rhythms and memory literature. My hope was that studying these genes might clarify some of the inconsistencies in past studies. I sought to answer a general research question: does hippocampal gene expression change when circadian rhythms are disrupted?

I hypothesized that significant differences in gene expression would be seen for some hippocampal genes. This would suggest a strong relationship between circadian rhythms and memory. Though past studies analyzed hippocampal gene expression changes in rats with intact versus disrupted circadian rhythms, my study was novel in two ways. Firstly, it is the first study that assessed circadian-related differences in hippocampal gene expression without using memory tasks, thereby establishing general genome-wide effects. Secondly, it is the first study that examined hippocampal gene expression changes every four hours in a 24-hour day, rendering my study the most detailed in tracking changes; past studies only looked at one to two timepoints in a 24-hour day.

Results showed that gene expression changed significantly in circadian-disrupted conditions for three of the eighteen genes analyzed. These were all genes associated with forming memories, learning, and having memory of everyday events. These findings show that circadian disruption may affect memory in these domains.

TS: Are there any future studies that will be conducted based on your method or results?

IH: Yes! After I completed my thesis manuscript, I sent it to Dr. Deibel and his colleagues to begin preparing it for publication. In the summer, Dr. Deibel hired a research assistant who began analyzing more genes in the dataset. The hope is to expand my thesis so that we can publish the most comprehensive work we can.

Also, given that some of the genes I analyzed had been well-studied in the context of memory but not circadian rhythms, I think it’s likely that my results about them will prompt further study in the circadian rhythms field. For example, I can imagine that researchers may choose to look at the activity of these genes during memory tasks in normal versus disrupted circadian conditions. This might help explain whether memory- related genes actually function differently in normal versus disrupted circadian conditions when doing memory tasks.

Another meaningful study that I think should follow this work is to repeat my study using a sample of female rats. It’s important to emphasize that differences in circadian rhythms have been observed across male and female rats, and my study only used male rats. To get a full picture of the relationship between circadian rhythms and memory, my study should be redone using female rats, and any notable differences in the findings should be very well-documented.

TS: What would you consider the most intriguing part of your research?

IH: The main thing that amazes me about this study is that the rats in the dataset underwent circadian disruption for seven days before they were sacrificed and their gene expression data collected. This means that all the differences in memory gene expression that I saw had manifested only over a seven-day span! Imagine what the implications of this means for how quickly circadian disruption can affect cognition. As a student well-acquainted with late-night studying and all-nighters, it was frightening to see that circadian disruption over only a week caused differences in genes associated with learning, memory formation, and memory of everyday events. Though parallels between rats and human studies are drawn tentatively, this result made me reflect differently on why I feel so unable to grasp any new information after months of self-inflicted, school-related insomnia. When I presented my work at UNB’s Honours Conference, this resonated with many of the people I spoke with, too. This idea becomes even scarier when I think about long-term night-shift schedules - especially for people who work high-risk jobs, like airplane pilots or truckers. In these jobs, lapses in memory could be fatal, and circadian disruption may very well play a huge role in it. Overall, I hope that the results of this study make people reflect on how important it is to maintain routines that align with their daytimes and nighttimes. Even a short span of misalignment could alter how we learn and maintain memory. The concreteness of seeing this alteration at the biological level is very striking.

TS: Is there anything else you wish to share about the research experience/ study?

IH: Only that it was incredibly fulfilling. I ultimately enjoyed the freedom I had in writing my thesis and doing data analysis. I also loved that I was able to apply a statistical analysis tool I learned about from my computational chemistry work to analyzing data for my honours thesis. It felt great to be in a flow where I could see how my experience in different fields could interact with each other. At the Honours conference, it was beautiful to see my colleagues’ presentations and presentation styles, with the knowledge of how everyone’s projects had evolved over the year. I think there was a nice sense of community established with my Honours class, especially as some of us traveled to Halifax together the next month to present our theses at a regional psychology conference. I’ll certainly look back on the whole year more fondly than not. Ψ

Created for The Synapse by Molly Miller.