Neurology Central

Enter the Honeycomb maze: a new gold standard for spatial navigation?

This month saw the publication of a paper in Nature describing a new test to study hippocampal-dependent spatial navigation: the Honeycomb maze. Designed to overcome challenges presented by current tests, the new maze has been in development for over a decade while different technologies and configurations were tested. The maze comes from the lab group of John O’Keefe, 2014 laureate of the Nobel Prize for his work on the discovery of place cells.
Here, we speak to Ruth Wood, MRC Clinical Research Training Fellow in the O’Keefe group at University College London (UCL; London, UK), and one of the lead authors on the paper describing the Honeycomb maze. Ruth discusses the maze, recent developments in systems neuroscience, and how these are being put to use across the spectrum of neuroscience research.

Can you tell us about the new Honeycomb maze? What was the basis for this research?

Certain brain regions represent spatial aspects of the environment, for example the entorhinal cortex and hippocampus encode spatial information through the activity of spatial cells such as “grid cells” and “place cells”. These brain areas support an animal’s ability to navigate to locations containing food and avoid locations containing danger. Mazes are widely used by neuroscientists to study brain function and rodent spatial behavior by asking them to travel to locations containing food rewards or avoid locations associated with aversive stimuli.

Several mazes are in current use but all have drawbacks. Many of the existing mazes produce only a binary (correct/incorrect) output, which makes them less useful for tracking the effects of progressive entorhinal and hippocampal pathology, for example in mouse models of Alzheimer’s disease. The popular T- and Y-mazes, the Olton radial arm maze and the Barnes maze can also be solved using more than one navigational strategy: a “directional-” or “object-heading” strategy, or a “place learning” strategy. The Morris water maze addresses this problem by forcing the animal to use a single identifiable navigational strategy, “place learning”, since the animal approaches the hidden goal from different directions and starting locations on each trial. However, it does not lend itself well to electrophysiological studies since it is a water-based task and there is no way to ensure that the animal evenly samples the whole maze environment.

The Honeycomb maze was specifically designed to overcome these limitations.

Interested in novel tests and spatial memory? Read Ruth’s previous interview on the development of the 4 Mountain’s Test for Alzheimer’s disease here

How does this new test overcome the drawbacks of existing tests for spatial navigation and memory?

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