New Tests in Mouse Models Enhance Cognitive Research
Innovative protocols improve understanding of cognitive functions in mice for human health.
Aimee Bertolli, Oday Halhouli, Yiming Liu-Martínez, Brianna Blaine, Ramasamy Thangavel, Qiang Zhang, Eric Emmons, Nandakumar S. Narayanan, Serena B Gumusoglu, Joel C. Geerling, Georgina M Aldridge
― 6 min read
Table of Contents
Neurodegeneration is a fancy term for the gradual loss of neurons in the brain, leading to conditions like dementia. This is no laughing matter, as about 55 million people around the world are struggling with various forms of dementia. It’s like a club nobody wants to join, but unfortunately, it’s growing.
The Mouse Models
To figure out what’s going wrong in our brains, scientists often use mouse models. Why mice, you ask? Mice have brain structures that are quite similar to ours. Plus, they are small, easy to handle, and there are tons of genetic tools available for experimenting. Using mice allows researchers to test new treatments and understand the underlying mechanisms of memory issues.
But here’s the catch: while much research focuses on memory, there are non-memory issues in dementia that often get overshadowed. For example, executive dysfunction is a common feature in different types of dementia, including Alzheimer’s and others. Think of executive dysfunction as losing your ability to plan your grocery list. It's annoying, isn’t it?
Testing Cognition in Mice
Behavioral tests in mice often involve tasks that check their memory and navigation skills. For instance, scientists use strategies like novelty exploration and finding escape routes. Tests like the Morris Water Maze or the Novel Object Recognition tasks help measure how well mice can remember things. But there's a problem. Many of these tests primarily look at short-term memory, even when researchers want to examine other cognitive aspects. It’s like walking into a bakery and only focusing on the donuts, ignoring the wedding cakes.
Barnes Maze
TheOne popular test for mice is the Barnes Maze. This clever design helps evaluate spatial memory, which is crucial for understanding how well animals can navigate their environment. Imagine a merry-go-round where mice are put in the middle of a circular platform with holes around the edge. One of these holes leads to a cozy escape box. Mice, being the little adventurers they are, have a natural urge to find that escape route.
The Barnes Maze has some excellent features: it resembles natural exploration, does not rely on food or water for motivation, and is relatively low-stress. Scientists love that it can even be adjusted for mice with motor issues, like the ones who can't swim.
The Challenges of Mouse Behavior
However, studying mouse behavior has its challenges. Mice can be finicky; they are highly sensitive to their surroundings. This sensitivity can lead to variations in how different groups of mice behave during tests, making it difficult to interpret the results. Sometimes, a small change in their environment can dramatically change their behavior. This is like trying to have a calm dinner party, but then your cat decides it’s time to play with the tablecloth.
Confounding Factors
Olfactory cues (that’s a fancy way of saying “smells”) can mess with the results. If mice can smell where the escape route is, they might find it more easily, masking their actual memory skills. Most labs stick with one escape box during all trials, which could make it easier for the mice to remember through smell rather than spatial learning. This raises some eyebrows because scientists want to ensure they are measuring what they think they are measuring.
Modifying the Barnes Maze
In light of these challenges, some researchers decided it was time to shake things up. They took a classic approach and enhanced the Barnes Maze to assess a broader range of cognitive functions. They created something called the FIELD protocol, which stands for “Find the Invisible Exit to Locate the Domicile.” It’s all about making the escape box a little harder to identify through smell and visual cues.
How It Works
In the FIELD protocol, researchers use 3D-printed escape boxes and adapt the original setup to ensure that the mice don’t get distracted by familiar smells. Imagine wearing a blindfold while playing hide and seek; it makes things interesting, doesn’t it? They even designed the setup to minimize the number of times a single escape box is used, breaking up the odor cues.
When they tested this new version, they found that mice still remembered where to go, but this time, they were really using their spatial learning skills instead of relying on their noses. This is excellent because it gives researchers a clearer picture of how well these little critters are learning.
Evaluating Cognitive Functions
The researchers also incorporated different stages in their testing. For example, they introduced the STARR FIELD protocol, which stands for "Spatial Training and Rapid Reversal." This new twist allows mice to show their Cognitive Flexibility. It’s a bit like asking your friend to navigate a new route to a restaurant. If they can figure it out quickly, they are showing good cognitive flexibility.
The Importance of Outcome Measures
Outcome measures are the criteria researchers use to assess how well the mice are completing tasks. They look at things like how long it takes a mouse to find the escape route (latency), the distance traveled, and how many times they visit the wrong holes. It’s like judging a race: you want to know who finished first and how well each competitor performed.
But researchers have to be careful. If they only focus on one measure, they might miss important details. The best approach is usually a combination of various outcomes, which can give them a complete picture of the mouse’s cognitive performance.
Real World Applications
Understanding how mice learn and remember can have significant implications for human health. If researchers can better identify cognitive deficits in mice, they may also uncover similar issues in humans. This information could lead to improved treatments and interventions for people facing neurodegenerative diseases.
The Challenges Ahead
Even though the FIELD protocol and STARR FIELD protocols are promising, there are still some limitations. The differences in motivation, fear, and exploration can influence the results. For instance, if a mouse is feeling a bit timid, it may not explore as much, affecting the outcome. Researchers must continue refining these methods and exploring new ones that can provide more reliable and consistent data.
Conclusion
In the battle against neurodegeneration and dementia, researchers are constantly seeking better ways to evaluate cognitive functions. By modifying existing tests like the Barnes Maze and employing innovative methods like the FIELD and STARR FIELD protocols, they are opening avenues for discovery. Ultimately, understanding how mice think and behave in these tests could help pave the way for breakthroughs in treatments for human cognitive decline.
So, here’s to our little furry friends doing the hard work, paving the way for smarter solutions in the world of neuroscience!
Title: Renovating the Barnes maze for mouse models of Dementia with STARR FIELD: A 4-day protocol that probes learning rate, retention and cognitive flexibility.
Abstract: Land-based mazes that require spatial cues to identify the location of a hiding-place are a low-stress method to evaluate learning rate and memory retention in mice. One version, the Barnes maze, allows quantification of naturalistic exploratory behaviors not evident in water-based tasks. As the task relies on innate behaviors, it does not require overtraining, making it more feasible to examine early learning and non-memory executive functions that are characteristic of some non-amnestic dementias. However, because it is difficult to hide odor cues in the traditional version of the maze, learning rate during individual trials can be difficult to interpret. We designed and tested the use of 3D-printed escape shuttles that can be made in duplicate, as well as a docking tunnel that allows mice to self-exit the maze to improve reproducibility and limit experimenter influence. In combination with maze turning and escape tunnel caps, we show our shuttles mitigate the possibility of undesired cues. We then compare use of our 4-day protocol across several mouse models of cognitive impairment. We demonstrate an additional stage, the STARR protocol (Spatial Training and Rapid Reversal), to better challenge executive functions such as working memory and behavioral flexibility. We examine commonly used outcome measures across mice with and without access to spatial cues, as well as across mouse models of cognitive impairment to demonstrate the use of our 4-day protocol. Overall, this protocol provides detailed instructions to build and perform a robust spatial maze that can help expand the range of deficits identified. Our findings will aid in interpretation of traditional protocols, as well as provide an updated method to screen for both amnestic and non-amnestic cognitive changes.
Authors: Aimee Bertolli, Oday Halhouli, Yiming Liu-Martínez, Brianna Blaine, Ramasamy Thangavel, Qiang Zhang, Eric Emmons, Nandakumar S. Narayanan, Serena B Gumusoglu, Joel C. Geerling, Georgina M Aldridge
Last Update: 2024-12-01 00:00:00
Language: English
Source URL: https://www.biorxiv.org/content/10.1101/2024.11.30.625516
Source PDF: https://www.biorxiv.org/content/10.1101/2024.11.30.625516.full.pdf
Licence: https://creativecommons.org/licenses/by/4.0/
Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.
Thank you to biorxiv for use of its open access interoperability.