To learn about how to improve the use of mazes in mouse research, ALN sat down with Shuhan He, MD, the founder of Maze Engineers, a company dedicated to improving the use of mazes in preclinical research.

ALN: How can mazes used in mouse research help advance human neurological study?
Shuhan He, MD (SH): There have been 33 phase III prospective clinical trials for human traumatic brain injury (any sort of pathology where people hit their head too hard), and a 100% failure rate, even though these drugs succeed in mice and rats. Currently, there are no drugs that exist for the majority of neurological disorders, ranging from strokes to concussions to traumatic brain injury to even things like Parkinsons and Alzheimers.

The thing is, the behavior of mice and rats is still the most important indicator in neuroscience. Behavior unifies all the other parts of the brain and body, and study after study shows they’re just not that different than humans.

Having good behavioral assessments is a key part to discovering new drugs and mazes help researchers do that. It helps us determine if mice are faster, better, stronger, smarter, or less anxious and afraid (in cases of depression and anxiety drugs).

ALN: What is the greatest challenge in using mazes in animal research?
SH: Good mazes can generally be thought of in two categories: 1) Easy to use and simple, or 2) Hard to use and complex. The more complex behaviors can be interpreted, the better. This means we can figure out higher levels of behavior like learning, memory which translate well to human quality of life. However, most of these are complex to use. Our job is to find mazes at the intersection of these categories: mazes that are easy to use and generate very useful behavioral data.

ALN: What can researchers do to improve research involving mazes in their laboratories?
SH: I have three suggestions for improving researching that involves mazes:

Looking at better mazes: there are a host of very useful mazes that are relatively low cost and incredibly useful. They generally are assays. One great example invented by Dr. Robert Deacon is called the “successive alleys test” and is a great test of anxiety, and I highly encourage scientists to use it over the elevated plus maze, which is more expensive and actually less useful.

Successive Alleys Test

Proper utilization: very popular tests such as the Morris water maze are really a great for learning but require mice and rats to have good visual acuity in order to test the learning aspect of the test. Often times, strains are used with the Morris water maze have very poor acuity, and the results show statistical significance. I always suspect these results may be incidental when this occurs.

The Morris water maze

Gender and experimenter uniformity: unfortunately many little things matter in the experiment. A person’s gender, color of clothing, time of day, housing environment, and especially perfume matter a lot to the results. Ensuring this is described well in the methods is incredibly important.

ALN: Is there anything else you would like to add?
SH: I think most researchers confine themselves to very few popularly used mazes. There is a whole world of really interesting behavioral paradigms that just get lost in the literature. I’ll give one example of this. There’s a single paper from 1989 that described a tilt ladder. In this paper, rodents were kept in a narrow chamber at an angle and the saphenous vein was measured to describe blood flow in this area of the rodent. This same apparatus could easily be used for very interesting motor function assays, but never did. I suspect that the next researcher who does utilize it properly could use it for very interesting assay results. Imagine a TBI experiment that marks, on a gradient, the restoration of function over time by measuring what angles mice or rats can climb as they rehabilitate with an adjuvant drug. This could be incredibly interesting science that is waiting to be done.