New Y-Maze Test May Be Useful Measure of Memory and Thinking Skills

A new behavioral test called the free-movement pattern Y-maze could be useful in assessing problems with working memory, both in animal models and people, a new study suggests.

It may also help with research into neurological diseases like Parkinson’s.

The study, “The Free-movement pattern Y-maze: A cross-species measure of working memory and executive function,” was published in Behavior Research Methods.

In Parkinson’s and other neurological conditions, problems with executive functions — like working memory and cognitive flexibility — are common. Research into these deficits requires reliable models in which to do experiments.

However, designing effective models for measuring memory in animals can be difficult. Many animal models are highly species-specific, making their relevance to human disease uncertain. And memory tests can  involve conditioning animals using an unpleasant stimulus such as a shock. There is a need for both more human-relevant and humane methods of measuring working memory.

Researchers designed a maze for this purpose, which they called the free-movement pattern (FMP) Y-maze. The maze itself builds off the Y-maze, an existing behavioral test that basically measures how much animals will explore parts of a maze they haven’t seen before.

The FMP Y-maze relies on a similar principle. Using specialized software, it measures the patterns of turns that animals take in the maze. For example, one animal might make a right turn, then two left turns, then another right turn; another animal might make four left turns in a row.

They first tested the FMP Y-maze on zebrafish. Analysis showed that the fish tended to follow certain patterns of turning — say, going right, then left, then right again (or vice versa) more often than other patterns. Importantly, the fish weren’t following these patterns based on cues they got from the maze or the researchers. Instead, they were acting based on previous actions in the maze — in other words, they were relying on memory.

“Our evidence strongly suggests that movement patterns were the result of a global strategy, relying on memory of past turn choices,” the researchers wrote. This suggests that the FMP Y-maze could be used to measure abnormalities in working memory.

Supporting this idea, when the researchers treated the fish with substances that affected memory, significant changes in some of the turning patterns were observed.

With their model validated in zebrafish, the researchers next developed versions of the FMP Y-maze for two other common laboratory animals: mice and fruit flies.

“Mice navigated the FMP Y-maze using an almost identical strategy to zebrafish,” the researchers wrote.

Fruit flies used a different strategy than the two vertebrate species, which the researchers speculated may be because flies will often explore by climbing on walls. Still, distinct patterns were evident in all species tested, suggestive of working memory at work.

Importantly, these patterns were seen without any external stimulus, like shocks or food rewards.

“It is very rare to find a non-invasive, humane test which can reliably improve diagnosis and be used to improve drug discovery using animal models of complex brain disorders that result in loss of memory and brain function,” Matt Parker, PhD, with the University of Portsmouth and a study co-author, said in a press release.

In a final experiment, a virtual version of the maze was explored by human volunteers.

“Humans used an almost identical strategy to mice and zebrafish,” the researchers wrote. “Our results demonstrate the suitability of the FMP Y-maze as a test of memory, not just for animals, but also for humans.”

As a measure of memory, the FMP Y-maze may be useful in screening for memory problems as part of a diagnosis, or it could be help in assessing how treatments affect memory. The researchers noted that specific protocols would need to be developed and validated for such applications.

“This has huge implications for the development of drugs to treat such [neurological] conditions,” Parker said. “The maze we developed lays the foundation of future research into a range of neurological disorders and could open new avenues of research into cognition and memory, allowing cross-species comparisons with exceptional translational relevance, minimal stress and reducing the number of test animals.”