A new statistical method to analyze Morris Water Maze data using Dirichlet distribution.

Marianne Maugard,Gilles Bonvento,Cyrille Doux

doi:10.12688/f1000research.20072.2

Abstract

The Morris Water Maze (MWM) is a behavioral test widely used in the field of neuroscience to evaluate spatial learning memory of rodents. However, the interpretation of results is often impaired by the common use of statistical tests based on independence and normal distributions that do not reflect basic properties of the test data, such as the constant-sum constraint. In this work, we propose to analyze MWM data with the Dirichlet distribution, which describes constant-sum data with minimal hypotheses, and we introduce a statistical test based on uniformity (equal amount of time spent in each quadrant of the maze) that evaluates memory impairments. We demonstrate that this test better represents MWM data and show its efficiency on simulated as well as in vivo data. Based on Dirichlet distribution, we also propose a new way to plot MWM data, showing mean values and inter-individual variability at the same time, on an easily interpretable chart. Finally, we conclude with a perspective on using Bayesian analysis for MWM data.

Highlights

The Morris Water Maze (MWM) was first described by Richard Morris in the 80’s 1 and is still one of the most commonly used tasks to evaluate spatial learning in rodents, including normal and genetically modified mice
We will first describe the methodology we developed with the Dirichlet distribution and the correction required to fit with the sample size of behavioral experiments
3.1 Application of the likelihood-ratio test based on the Dirichlet distribution We compared the distribution obtained for each group to a uniform distribution in the probe test of the standard reference memory task and we found that the Dirichlet distribution obtained for wild-type mice was significantly different from a uniform distribution (p = 0.0021), whereas the one obtained for 3xTg mice did not differ from a uniform distribution (p = 0.26)

Summary

Introduction

The Morris Water Maze (MWM) was first described by Richard Morris in the 80’s 1 and is still one of the most commonly used tasks to evaluate spatial learning in rodents, including normal and genetically modified mice. While the standard reference memory task is mostly used and is validated as an assay for hippocampus-dependent spatial navigation and reference memory, modifications of the basic protocol allow to evaluate reversal learning, the delayed match to place task and procedures for dissociating encoding and retrieval. At least for the standard reference memory and reversal learning tasks, these procedures require probe test data that display a constant-sum constraint. The maze consists of a large circular tank filled with opaque water in which rodents can escape onto a platform hidden just beneath the surface. Since data are right-truncated at 60 seconds, in contradiction with a normal distribution and causing potentially biased results, statistical guidelines have been published to properly characterize learning behaviors using survival data 2

Results

Discussion

Conclusion