a case study of memory loss in mice answers

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A Case Study of Memory Loss in Mice

By Michael S. Hudecki (rr)

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This discussion case explores the scientific process involved in implementing an animal model in the study of Alzheimer’s disease. Students read a short paragraph describing a study in which the brains of “trained” mice were injected with beta-amyloid fragments, which subsequently caused them to forget their tasks. The paragraph is a very short New York Times story reporting on an experimental study originally published in the Proceedings of the National Academy of Sciences . Based on the short description provided, students are asked to identify relevant components of the scientific method (problem, method, results, and conclusions). The case is suitable for a wide variety of science majors and non-majors courses.

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Date Posted

• To demonstrate the scientific method in action.
• To explore the workings of the nervous system in health and disease, with specific attention given to the degenerative disorder, Alzheimer’s disease.
• To understand that important advances in human disease research often rely on carefully crafted and implemented animal model systems.

Alzheimer’s disease; alzheimers; nervous system; animal model systems; preclinical animal studies; Food and Drug Administration; FDA; beta-amyloid; memory loss; experimental design

Subject Headings

EDUCATIONAL LEVEL

High school, Undergraduate lower division

TOPICAL AREAS

Scientific method

TYPE/METHODS

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Answer Keys are protected and access to them is limited to paid subscribed instructors. To become a paid subscriber, purchase a subscription here .

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Scientists reverse age-related memory loss in mice

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Scientists at Cambridge and Leeds have successfully reversed age-related memory loss in mice and say their discovery could lead to the development of treatments to prevent memory loss in people as they age.

Although our study was only in mice, the same mechanism should operate in humans – the molecules and structures in the human brain are the same as those in rodents. This suggests that it may be possible to prevent humans from developing memory loss in old age James Fawcett

In a study published in Molecular Psychiatry , the team show that changes in the extracellular matrix of the brain – ‘scaffolding’ around nerve cells – lead to loss of memory with ageing, but that it is possible to reverse these using genetic treatments.

Recent evidence has emerged of the role of perineuronal nets (PNNs) in neuroplasticity – the ability of the brain to learn and adapt – and to make memories. PNNs are cartilage-like structures that mostly surround inhibitory neurons in the brain. Their main function is to control the level of plasticity in the brain. They appear at around five years old in humans, and turn off the period of enhanced plasticity during which the connections in the brain are optimised. Then, plasticity is partially turned off, making the brain more efficient but less plastic.

PNNs contain compounds known as chondroitin sulphates. Some of these, such as chondroitin 4-sulphate, inhibit the action of the networks, inhibiting neuroplasticity; others, such as chondroitin 6-sulphate, promote neuroplasticity. As we age, the balance of these compounds changes, and as levels of chondroitin 6-sulphate decrease, so our ability to learn and form new memories changes, leading to age-related memory decline.

Researchers at the University of Cambridge and University of Leeds investigated whether manipulating the chondroitin sulphate composition of the PNNs might restore neuroplasticity and alleviate age-related memory deficits.

To do this, the team looked at 20-month old mice – considered very old – and using a suite of tests showed that the mice exhibited deficits in their memory compared to six-month old mice.

For example, one test involved seeing whether mice recognised an object. The mouse was placed at the start of a Y-shaped maze and left to explore two identical objects at the end of the two arms. After a short while, the mouse was once again placed in the maze, but this time one arm contained a new object, while the other contained a copy of the repeated object. The researchers measured the amount of time the mouse spent exploring each object to see whether it had remembered the object from the previous task. The older mice were much less likely to remember the object.

The team treated the ageing mice using a ‘viral vector’, a virus capable of reconstituting the amount of 6-sulphate chondroitin sulphates to the PNNs and found that this completely restored memory in the older mice, to a level similar to that seen in the younger mice.

Dr Jessica Kwok from the School of Biomedical Sciences at the University of Leeds said: “We saw remarkable results when we treated the ageing mice with this treatment. The memory and ability to learn were restored to levels they would not have seen since they were much younger.”

To explore the role of chondroitin 6-sulphate in memory loss, the researchers bred mice that had been genetically-manipulated such that they were only able to produce low levels of the compound to mimic the changes of ageing. Even at 11 weeks, these mice showed signs of premature memory loss. However, increasing levels of chondroitin 6-sulphate using the viral vector restored their memory and plasticity to levels similar to healthy mice.

Professor James Fawcett from the John van Geest Centre for Brain Repair at the University of Cambridge said: “What is exciting about this is that although our study was only in mice, the same mechanism should operate in humans – the molecules and structures in the human brain are the same as those in rodents. This suggests that it may be possible to prevent humans from developing memory loss in old age.”

The team have already identified a potential drug, licensed for human use, that can be taken by mouth and inhibits the formation of PNNs. When this compound is given to mice and rats it can restore memory in ageing and also improves recovery in spinal cord injury. The researchers are investigating whether it might help alleviate memory loss in animal models of Alzheimer's disease.

The approach taken by Professor Fawcett’s team – using viral vectors to deliver the treatment – is increasingly being used to treat human neurological conditions. A second team at the Centre recently published research showing their use for repairing damage caused by glaucoma and dementia .

The study was funded by Alzheimer’s Research UK, the Medical Research Council, European Research Council and the Czech Science Foundation.

Reference Yang, S et al. Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing. Molecular Psychiatry ; 16 July 2021; DOI: doi.org/10.1038/s41380-021-01208-9

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Researchers Reverse Trauma-Induced Memory Loss in Mice

by Denis Storey January 19, 2024 at 12:03 PM UTC

Clinical Relevance: Georgetown conducted a study in partnership with Trinity College Dublin, Ireland, indicating that memory loss from repeated head trauma, similar to that endured by NFL players, might be reversible in mice.

• The research, published in the Journal of Neuroscience , suggests that amnesia and poor memory following head injury result from inadequate reactivation of neurons involved in forming memories, and the condition may not be a permanent pathological event.
• Previous studies by the team revealed that the brain adapts to recurrent head trauma by altering synapse firing, making it difficult to forge new memories.
• The research demonstrated the potential for mice to recall lost memories, offering hope for designing treatments to recover cognitive function in humans with poor memory due to repeated head impacts.

As we creep closer to the closest thing this country has to a national sports holiday, some promising news on head trauma has emerged from Georgetown University Medical Center. A new study of mice shows that the memory loss from repeated head trauma – like the kind NFL players endure – might be reversible.

Specifically, Georgetown’s research, conducted in partnership with Trinity College Dublin, Ireland, reveals that “amnesia and poor memory following head injury is due to inadequate reactivation of neurons involved in forming memories.”

The findings , appearing in the latest issue of the Journal of Neuroscience , show that the memory loss caused by head injuries isn’t “a permanent pathological event driven by a neurodegenerative disease.” The researchers found that they were able to counter the amnesia, which enabled the mice to recall their lost memories, “potentially allowing cognitive impairment caused by head impact to be clinically reversed.”

Following Up Earlier Findings

This isn’t the team’s first foray into the brain’s resiliency. In an earlier study, the researchers discovered that the brain adapts to recurrent head trauma by altering the ways its synapses fire. This simple adaptation makes it increasingly difficult for the brain to forge new memories and recall more recent ones.

This promising new research showed the team that they could prompt mice to recall memories once thought lost because of head trauma.

“Our research gives us hope that we can design treatments to return the head-impact brain to its normal condition and recover cognitive function in humans that have poor memory caused by repeated head impacts,” the study’s senior investigator, Mark Burns, PhD, a professor and vice chair in Georgetown’s Department of Neuroscience and director of the Laboratory for Brain Injury and Dementia, explained in a press release.

Methodology

In this latest research, the team helped two groups of mice build a new memory by running them through a test they hadn’t been through. The researchers then subjected one group “to a high frequency of mild head impacts for one week (similar to contact sport exposure in people) and one group were controls that didn’t receive the impacts.”

Unsurprisingly, the injured mice couldn’t recall the new memory a week later.

“Most research in this area has been in human brains with chronic traumatic encephalopathy (CTE), which is a degenerative brain disease found in people with a history of repetitive head impact,” Burns explained. “By contrast, our goal was to understand how the brain changes in response to the low-level head impacts that many young football players regularly experience.”

Mimicking Football Player Trauma

Established research has found that, on average, college football players endure more than 20 head impacts a week, with defensive ends receiving more than 40. 

So the Georgetown scientists designed the frequency of head impacts on mice to replicate a week of exposure for an “average” college football player.

The researchers leveraged genetically modified mice to observe the neurons involved in forming new memories. As a result, they discovered that “these memory neurons (the “memory engram”) were equally present in both the control mice and the experimental mice.”

To better grasp the physiology behind these memory shifts, one of the study’s authors, Daniel P. Chapman, PhD, said, “We are good at associating memories with places, and that’s because being in a place, or seeing a photo of a place, causes a reactivation of our memory engrams. This is why we examined the engram neurons to look for the specific signature of an activated neuron. When the mice see the room where they first learned the memory, the control mice are able to activate their memory engram, but the head impact mice were not. This is what was causing the amnesia.”

The researchers reversed the amnesia with lasers to trigger those engram cells.

“We used an invasive technique to reverse memory loss in our mice, and unfortunately this is not translatable to humans,” Burns said. “We are currently studying a number of noninvasive techniques to try to communicate to the brain that it is no longer in danger, and to open a window of plasticity that can reset the brain to its former state.”

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Chronic Traumatic Encephalopathy and Sports

“There’s No Crying in Football!”

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Sleepy Mice Case Study: Implementation and Assessment

Monica m. gaudier-diaz.

1 Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC 25799

Shveta V. Parekh

Rachel e. penton, sabrina d. robertson, aeisha thomas.

2 Department of Biological and Health Sciences, Crown College, St. Bonifacius, MN 55375

Case studies are a valuable teaching tool to engage students in course content using real-world scenarios. As part of the High-throughput Discovery Science & Inquiry-based Case Studies for Today’s Students (HITS) Research Coordination Network (RCN), our team has created the Sleepy Mice Case Study for students to engage with RStudio and the Allen Institute for Brain Science’s open access high-throughput sleep dataset on mice. Sleep is important for health, a familiar concern to college students, and was a basis for this case study. In this case, students completed an initial homework assignment, in-class work, and a final take-home application assignment. The case study was implemented in synchronous and asynchronous Introductory Neuroscience courses, a Biopsychology course, and a Human Anatomy and Physiology course, reflecting its versatility. The case can be used to teach course-specific learning objectives such as sleep-related content and/or science data processing skills. The case study was successful as shown by gains in student scores and confidence in achieving learning objectives. Most students reported enjoying learning about sleep deprivation course content using the case study. Best practices based on instructor experiences in implementation are also included to facilitate future use so that the Sleepy Mice Case Study can be used to teach content and/or research-related skills in various courses and modalities.

Case study-based learning is a high-impact approach that develops students’ science process, problem solving, and critical thinking skills. The case study method can be implemented in a variety of ways, but at its core, case-based teaching uses a real-world narrative to engage students in collaboration to solve problems and build analytical skills in a self-directed way. Case studies that combine real research data with relatable narratives also require students to apply quantitative skills, evaluate problems from a variety of perspectives, and consider the human impact of science. The case study approach, therefore, is a powerful tool for neuroscience and other classrooms that aligns with core competencies outlined by Vision and Change ( American Association for the Advancement of Science, 2011 ).

High-throughput research utilizes automation, technological advances, and large-scale experimentation to facilitate discovery. In the field of neuroscience, high-throughput research can take a variety of forms such as single neuron transcriptomics ( Boldog et al., 2018 ; Bandler et al., 2022 ; Yang et al., 2022 ), automated image analysis ( Thompson et al., 2010 ), proteomics ( Perkel, 2021 ; Yang et al., 2021 ; Paulsen et al., 2022 ), connectomics ( Zhang et al., 2020 ), genomics ( Janssens et al., 2022 ), and drug discovery ( Bock et al., 2021 ; Willsey et al., 2021 ). Combining various high-throughput approaches to tackle long-standing questions in the field is also becoming increasingly common ( Paulsen et al., 2022 ). Consequently, high-throughput approaches are transforming the way neuroscience research is conducted, requiring a matched evolution of our future neuroscientist training. Case studies that incorporate large, complex datasets offer an evidence-based approach to bolster student quantitative skills while also integrating high-throughput discovery into curricula. Creating such cases, however, is challenging given a variety of barriers such as limited faculty time, required training, and access to high-throughput technology, among others ( Williams et al., 2019 ).

HITS (High-throughput Discovery Science and Inquiry-based Case Studies for Today’s Students), a research coordination network sponsored by the National Science Foundation ( Robertson et al., 2021 ), aims to encourage integration of high-throughput discovery science into classrooms through the use of case studies. The network has implemented high-throughput-based case studies in over 18 different courses, reaching thousands of students at a diversity of institutions. Cases are created through working groups of high-throughput researchers and educators whose goal is to design, assess and share their cases broadly with the educational community. The current case was developed by an interdisciplinary HITS case fellow team. HITS fellows commit to the creation of a new high-throughput case, in return the network provides training, structured time, and financial support for case development. Our case fellow group saw a need for introductory level cases that require R programming and general quantitative skill development. As neuroscience and physiology instructors, we chose to focus on the topic of sleep.

We selected the topic of sleep for two primary reasons: (1) sleep deprivation is a scourge of modern society that has deadly consequences especially for the typical college-aged student and (2) the Allen Institute for Brain Science offers an open access high-throughput gene expression dataset based on a sleep deprivation study in mice ( Allen Institute for Brain Science, 2007 ; Thompson et al., 2010 ). Chronic sleep deprivation increases risk of all-cause mortality and risk of cardiovascular disease, neurodegenerative disease, depression, and car accidents, among others ( Cappuccio et al., 2010 ; Yin et al., 2017 ; Zamore and Veasey, 2022 ). In fact, sleep deprivation is a major risk factor for two of the top three most common causes of death for individuals aged 15 to 25, suicide ( Harris et al., 2020 ) and car accidents ( American Academy of Sleep Medicine Board of Directors et al., 2015 ; Gottlieb et al., 2018 ; Tefft, 2018 ; CDC, 2022a ; National Highway Traffic Safety Administration, 2022 ). Sleep deprivation is also detrimental to memory function, attention, and emotional regulation ( Alhola and Polo-Kantola, 2007 ; Chee and Chuah, 2007 ; Saghir et al., 2018 ); all critical brain functions for successful academic performance. Yet, college students report alarming rates of sleep deprivation ( Hershner and Chervin, 2014 ; CDC, 2022b ). Sacrificing sleep time is routine for students juggling academics, extracurriculars, jobs, key social needs, and more. As neuroscientists, we must educate students and our community on the devastating consequences of sleep deprivation. Our case meets this need by engaging students in a tale of sleep deprivation while also bolstering student quantitative and science process skills through the collection and analysis of a real sleep deprivation high-. throughput data set readily available through the Allen Brain Institute

CASE OVERVIEW

The case was designed to reinforce knowledge of sleep and the consequences of sleep deprivation, expose students to primary scientific literature as well as R, and require students to apply knowledge learned in class to their personal lives. The case included three parts: pre-case work, class activities, and post-case reflection. Students independently completed pre-case work which consisted of researching and summarizing how sleep deprivation can affect attention, emotion, memory or neurological diseases from primary scientific literature. Additionally, students downloaded R and used this program to explore the sleep deprivation literature and create a histogram of sleep deprivation papers through 2021. During the in-person class sessions, students typically worked in groups to collect gene expression data from the Allen Mouse Brain Atlas in an excel sheet, import data into RStudio, and use R to create a graph comparing brain gene expression in sleep-deprived and control conditions. Students were challenged to analyze their results to determine if there were any specific patterns of gene expression between control animals and sleep-deprived animals, as well as patterns specific to a brain region. For the in-class sessions held remotely, students completed class activities individually. Post-case reflections were completed individually and allowed students to apply their knowledge to their own lives by writing a letter to enact local policy change in school times as well as evaluating their sleep hygiene practices. This case would be appropriate for a neuroscience, psychology, or biology course that includes a unit on sleep biology and/or for the development of science data processing skills.

CASE IMPLEMENTATION

The Sleepy Mice Case Study was designed during Summer 2021 and implemented during Fall 2021 in a series of courses: Biopsychology (1 section) and Introduction to Neuroscience (3 sections) at the University of North Carolina at Chapel Hill and Human Anatomy and Physiology I (2 lab sections/joint lecture) at Crown College. During the

Fall 2021 implementation, 418 college students with a variety of declared majors were enrolled in these courses and were assigned the Sleepy Mice Case Study ( Table 2 ). The Sleepy Mice Case Study was implemented in the Introduction to Neuroscience course at University of North Carolina a second time in Spring 2022 (300 students in 2 sections), and a third time in Summer 2022 (40 students in 2 sections). Thus far, 768 students have been assigned the Sleepy Mice Case Study in a total of 9 sections of 5 courses. Student outcome data for this paper were only collected during the Fall 2021 implementation.

Case Implementation Course Parameters. Summary of parameters across courses in which the Sleep Mice Case Study was implemented.

Biopsychology

In-person with no remote option (1 section).

Implementation of this case differed slightly from others as pre-work, in-class work, and post-work were all completed in groups of 5–6 students. All students in the course completed all three elements of the case. Students divided work such that only one student from each group completed the R section of pre-work. A bulk of the R section pre-work includes instructions on downloading R and familiarizing themselves with the program. Groups’ ability to engage with R immediately in class was hampered because multiple group members were unfamiliar with R. Therefore, subsequent implementations of the case required the pre-work to be done on an individual basis to ensure all students downloaded R and used it before class. Despite this initial setback, at the end of class, all groups submitted a bar graph of mean in situ hybridization (ISH) values of their gene of interest.

In the post-case reflection, about 75% of students reported enjoying working with RStudio to generate a bar graph while about 25% of students reported that working with RStudio was confusing and difficult. Students cited other enjoyable aspects of the case, including searching for and reading literature related to sleep deprivation, connecting the material to their sleep practices, and the change from lecture to an activity. Other less enjoyable parts for students were writing the policy letter and the volume of work required.

Introduction to Neuroscience

Remote, asynchronous (1 section).

Students were responsible for completing the pre-case work individually, class activities in groups of 3–4 students, and post-case reflection individually. Approximately half of the students in the course (46%) completed all three elements of the case study. This was unusual for a lesson in the class but is likely because the lowest 20% of assignments in the class pre-work and engagement grade categories of the course are dropped from students’ final grades. Also, this lesson was implemented just before the third mid-term exam.

All 72% of students who completed the pre-case activity researched and summarized literature about sleep deprivation and their disorder of choice, but only 73% of those students submitted the literature histogram they created using Rstudio, while 26% did not. Of the 60 students who completed the post-case reflection, half reflected on using Rstudio: 50% reported enjoying working with Rstudio the most out of the activities and the other 50% reported enjoying working with Rstudio the least out of the activities. Other most enjoyable parts of the case study for students were connecting with Nadia, the character in the narrative, and looking for information about sleep deprivation. Other least enjoyable parts of the case study for students were working in groups and the volume of work required by the case study activities. Using Rstudio was a divisive point in the case study for students and may reflect the different proportion of majors in this section compared to other sections. An alternative interpretation is that implementing the case study asynchronously was a barrier for students trying to work with Rstudio.

In-person, Combination of Asynchronous and Synchronous Work (2 Sections)

For implementation, students completed the pre-case work individually and the class activities in groups of 4–6 students. The post-case reflection was also completed as a team. More than 85% of students participated and submitted the case study work. The increased case participation in these in-person versions of NSCI 175 is interesting. More students may have participated because the opportunity to work with their team in person made the Rstudio work less intimidating. Again, a key implementation strategy for our synchronous offerings of the case was to require students to individually complete the pre-work. This ensured that the majority of students had successfully downloaded R and created a histogram before our classroom activity day. In the 50-minute class period, the majority of student groups had a data figure exploring their gene of interest expression before leaving for the day. In the 75-minute class period, all groups completed the in-class activity and many had finished the post-class reflection.

A total of 87% of student groups reported enjoying the case study. Students cited a variety of aspects of the case as the most enjoyable: using R studio to conduct data analysis and create graphs, having the freedom to choose what genes to analyze, working with real data, collaborating with their peers, and learning about sleep deprivation. Students also mentioned how using a story (i.e., the case narrative) was more engaging than just a list of questions. Students’ least favorite aspects of the case included struggling with R studio and understanding the purpose of the coding steps as novices, writing the letter, the time required for the in-depth case, particularly the pre-work, the timing of the case study (on the last day of class for one section and right before an exam for the other) and the tedious process of gathering and organizing data from the brain atlas.

The majority, 93% of student groups, also reported a commitment to change their sleep practices to achieve better sleep hygiene and avoid the consequences of sleep deprivation, although many students pointed out the practical constraints to adopting better sleep hygiene when many students juggle academics, work, and extracurriculars. ​ extracurriculars.

Cumulative Major Demographics of Students in Fall 2021 Implementation. The overall percentage of students in all of our courses with each major. N = 418 students

Human Anatomy & Physiology I

In-person (1 section).

The students were given the pre-case work as a take-home assignment to complete. In this iteration, some of the students had computer-related issues and so a part of a subsequent lab was then used to help resolve these issues before moving on to the next step. The goal was to get everyone to the step where they had generated the graph using R. The students then completed the in-class work using the Allen Mouse Brain Atlas during a 50-minute lecture and this was enough time for some students but not all. The students subsequently submitted the graphs, graph analysis, and the letter writing assignment as part of the post-case reflection. The use of this activity in a non- Neurobiology course highlights that it can be used in multiple course contexts, even with students with minimal content background knowledge.

CASE ASSESSMENT

Participant recruitment and data collection procedures were reviewed and exempted by the University of North Carolina at Chapel Hill Institutional Review Board (PROTOCOL #21-2266). This UNC-exempted IRB protocol was then reviewed and approved by the Crown College Institutional Review Board. Quantitative and qualitative data were collected from student work submitted as part of the Sleep Mice Case Study implementation and an anonymous post-case study survey. The post-case study survey assessed student enjoyment ( Figure 1 ) and student perceptions on the achievement of learning outcomes ( Figure 2 ), whereas quiz/exam questions assessed content knowledge gained ( Figure 3 ). This assessment data only includes data from Introduction to Neuroscience and Biopsychology students.

Student perceptions of the case study. Students responded with strongly agree (blue), agree (light blue), neither agree nor disagree (grey), disagree (light red), or strongly disagree (red) to five statements about the case study. The five statements are on the left and corresponding cumulative bar plots are on the right (n = 192 students).

Retrospective Student Perceptions of the Achievement of Learning Outcomes. Students retrospectively responded with strongly agree (blue), agree (light blue), disagree (light red), or strongly disagree (red) to nine statements of confidence in their ability to meet Learning Objectives before and after completing the case study. The statements are on the left and corresponding cumulative bar plots are on the right (n = 182 students, Friedman with Dunn’s Multiple Comparisons Test, ****p< 0.0001).

Student scores on a short content quiz were improved following the case study. A . The fraction of students correctly answering three questions on a content quiz given pre-case and post-case (n = 276 students; Repeated Measures One-Way ANOVA, F = 70.73, ****p < 0.0001; Šidák’s multiple-comparisons test ****p < 0.0001 for each pre-case vs. post-case comparison). B . The average overall quiz score for students pre-case and post-case (n = 276 students; two-tailed paired t-test, ****p < 0.0001). Error bars are +/− SEM

Figure 1 summarizes student feelings and enjoyment of the case. Eighty-two percent of students strongly agree/agree that they enjoyed learning about sleep deprivation in the case format while only 45% strongly agree/agree they would have preferred a lecture. A majority of students (58%) also strongly agree/agree that they gained more knowledge about sleep deprivation from the case study format than from our textbook or lecture. Writing a persuasive letter was enjoyed and disliked by almost identical proportions of students 39%, and 22% felt neutral about this requirement of the assignment. A strong majority of students (70%) felt the case should be used again to learn about sleep deprivation, while only 11% felt it should not. In summary, the majority of students enjoyed the case format and felt they learned more from this pedagogical approach. Students were divided in their enjoyment of the letter writing, and many students mentioned this as a time-consuming aspect of the case in our open-ended questions. Accordingly, instructors should consider whether letter writing is essential for their classrooms and whether it aligns with their overall learning objectives and course goals.

To assess perceptions on the achievement of learning outcomes ( Figure 2 ), students were asked to retrospectively rate their confidence level for each of the case study learning objectives with the exception of “reading and interpreting primary literature”. When students compare their perceptions from before and after completion of the Sleepy Mice Case Study, they report significant increases in confidence for all content and skill-related learning objectives.

To assess content knowledge gains ( Figure 3 ), we had our students complete three multiple-choice content questions in the form of a quiz before covering the Sleep units. The same questions were later administered as part of an exam. For each question, we tallied the total correct responses and compared the values before and after the implementation of the case study.

The first two multiple choice questions focused on sleep biology content and the third on assessing their ability to interpret results and analyze a figure similar to the graphs generated in the case study assignment. Paired data were obtained from 276 students. The fraction of students answering each question correctly increased for all 3 questions and these increases were all statistically significant using Sidak’s multiple comparison test ( Figure 3 ). The overall quiz score also increased from 46.14% +/− 1.98% to 67.25% +/− 1.42% and this change was statistically significant using a two-tailed paired t-test ( Figure 3 ).

CONCLUSIONS

After integrating our case in five distinct classrooms, we compiled a summary of best practices ( Table 4 ). First, we highly recommend that instructors carefully consider the timing of case implementation during the semester. There is significant time, both in and out of the classroom, required for the case. Ensuring that other major course assignment deadlines or exams are not near the case study due dates is key. We also found students struggled to fully engage with the case when it was offered in the last week of class. Communication about the assignment is also essential. All of our courses are highly structured. For example, in Introduction to Neuroscience , students are required to read the text and take a quiz before each class session. The case study, however, breaks this tradition. Many students suggested that advanced discussion of the case requirements and posting of case materials would have been beneficial. We also compared how the case was delivered across our classrooms. Using a combination of asynchronous pre-work and synchronous class sessions yielded the best results. Every student, on their own, should watch an Rstudio tutorial video and download R to create a graph prior to class. Also, offering an office hour for R troubleshooting prior to the synchronous session will ensure that students arrive to synchronous session ready to collaborate or troubleshoot roadblocks they encountered with R. During the synchronous session, it is ideal if the instructors and assistants can circulate in the room or online break rooms to check in with all the groups. As an instructor, building your confidence with R is also important. Some of us were novice R users but by working through the case on our own we were adequately prepared to lead the synchronous session and troubleshoot. Instructors and students should also be aware that R and RStudio program updates may alter the steps listed in the student handout over time. Recruiting learning assistants that have significant R experience can also be valuable, especially for large classroom environments as they can circulate and assist students.

Summary of Best Practices.

In summary, our team created the Sleepy Mice Case Study as a part of the HITS network to develop student quantitative skills while exposing them to the power of high-throughput approaches, R Studio, and the Allen Institute for Brain Science’s open access datasets. We also used the case to convey the central role of sleep to human health and the significant consequences of sleep deprivation with hopes of impacting student sleep hygiene. By implementing the case in synchronous and asynchronous Introductory Neuroscience courses, a Biopsychology course, and a Human Anatomy and Physiology course, we’ve demonstrated its versatility. We’ve assessed our case, illustrating its ability to increase student scores and confidence in achieving learning objectives. Our students also generally enjoyed learning about sleep deprivation through the case study and many reported a commitment to change their sleep practices. We welcome adoption or adaptation of the Sleep Mice Case Study. The classroom implementation notes, full case narrative, and answer key are available upon request from [email protected] . Instructors seeking additional case information are encouraged to contact any of the co-authors.

Content and Skills Learning Objectives for the Sleepy Mice Case Study. Next to each learning objective is the associated assessment question.

This work was supported by the HITS Case Network (NSF-RCN Grant #1730317). The authors thank the graduate student instructional assistants, the undergraduate learning assistants, and students in Introduction to Neuroscience (NSCI 175) and Biopsychology (PSYC 220) at UNC Chapel Hill, and Human Anatomy and Physiology I (SCI 261) at Crown College, for their participation. The authors also thank Dr. Keith Shockley for his permission to use his code for the Case Study R literature histogram pre-work and Kaitlyn Casimo for her help accessing the Allen Mouse Brain Atlas Sleep Study data.

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The aging brain: New research paves way for treating memory loss

• The activity of the brain changes throughout a human lifetime , and one risk associated with old age is loss of memory and dementia.
• A new study in mice published in Nature has revealed that cerebrospinal fluid (CSF) could hold the key to understanding how and why the brain changes as we age.
• Understanding the biochemistry that underlines brain aging could help identify treatments for dementia.

Just 3 years ago the United States Food and Drug Administration (FDA) issued a warning against using plasma from young people in unproven treatments marketed at older people.

The existence of these unproven therapies was due to rumours based on misunderstood results from research in mice. One such study found that blood plasma infusions from young mice improved the memories and function of older mice.

Further experimentation in humans has also failed to show an effect. A 2017 trial showed infusions of blood plasma from young people did not reduce Alzheimer’s symptoms in older people, for example.

CSF bathes the brain and serves three key functions: cushioning it from knocks, providing it with nutrients, and removing waste.

This new study in Nature aimed to study whether transferring CSF, rather than plasma, from younger to older mice might affect brain aging.

Transferring CSF between mice

To start this experiment researchers had to condition the mice to remember an event so they could test this memory later. Twenty-month-old mice were given 3 electric shocks on their foot at the same time as being exposed to a tone and a flashing light, to help create an association.

These older mice then had cerebrospinal fluid from 10-week-old mice injected into them for a week. A control group received artificial CSF.

Three weeks later, the researchers tried to ascertain how this affected the mice’s memory. To do this, they exposed the mice to the same tone and flashing light but without the electric shocks, and many froze with fear.

However, mice that received CSF from young mice froze in fear almost 40% of the time, compared to 18% of the time in mice given artificial CSF.

This suggested the CSF from young mice was having a rejuvenating effect on the older brains, which improved their memory.

Growth factors and differentiation of cells

Further experiments showed that the CSF of young mice was boosting the proliferation and differentiation of cells that turn into a type of central nervous system cell called oligodendrocytes. Repeated experiments with human CSF showed a similar, but lesser effect.

A key role of oligodendrocytes is to produce a fat-rich substance called myelin. Myelin forms a protective sheath around nerves, which insulates them and therefore allows the nerves to rapidly communicate electrical impulses.

In addition to more oligodendrocytes, mice receiving young CSF had more myelin coated nerves in their hippocampus , a part of the brain essential for memory. The authors suggest this led to improved nerve conduction in the hippocampus and therefore improved memory in the treated mice.

Further analysis to understand the changes pointed to the role of fibroblast growth factor 17, a protein that is commonly expressed in the brain but declines with age. The study showed this growth factor was necessary and sufficient to create more oligodendrocytes and to improve memory and cognition in mice.

Implications for treating dementia

Dr. Rebecca Edelmayer , senior director of scientific engagement at the Alzheimer’s Association told Medical News Today in an email that the paper was “intriguing but very preliminary.”

She said: “For those of us working on Alzheimer’s disease and other dementia, there is much we can learn from the process of normal aging by studying the natural changes that occur in the brain over time. For example, can replenishing factors that naturally diminish over time be used to protect against or reverse neurodegenerative disease processes like Alzheimer’s?”

She added: “The idea of replenishing growth factors to support cellular health is not new. Research studying cellular growth factors is a common area of neuroscience, and it is being investigated for multiple diseases.”

Dr. Rosa Sancho , head of research at Alzheimer’s Research U.K. agreed that the findings were interesting, but that the research was very early stage. She told Medical News Today in an interview: “What was nice in the studies is that they’ve identified a couple of proteins that could be involved in this mechanism.”

“And it’s really important actually, that we identify these new avenues for translational research. As you know, there are no disease-modifying treatments in the U.K. for people with dementia. At the moment, they only have access to symptomatic treatments.”

Identifying molecules that could be treatment targets could be key to developing drugs in future, she explained.

“It’s very early-stage research in mice, but I think it does have a lot of interest and a lot of potential to be further replicated and developed.” – Dr. Sancho

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A Case Study of Memory Loss in Mice

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Using a short news article, high school or college biologists examine the scientific method in practice. The article, which focuses on an Alzheimer's experiment performed on rats, has very limited information, so learners must be able to draw inferences in order to answer the questions on the handout.

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