Validation of the dimensionality emergence assay for the measurement of innate anxiety in laboratory mice

Abstract

The open field test is a common tool to measure innate anxiety in rodents. In the usual configuration of this test the animal is forced to explore the open arena and its behavior includes both anxiety and non-anxiety responses. However, the open arena is generally small and allows only limited expression of exploratory behavior. The recently developed dimensionality emergence assay in which an animal is housed in a home cage with free access to a large circular arena elicits graded exploration and promises to serve as a more ethological test of anxiety. Here we examined the predictive validity of this assay for anxiety-related measures in mice. First, we compared their behavior in the presence or absence of access to the home cage and found that mice with access to the home cage exhibited a gradual build-up in exploration of the arena while those without did not. Then we identified behavioral measures that responded to treatment with the anxiolytic drug diazepam. Diazepam altered several classical measures of innate anxiety, such as distance traveled and thigmotaxis, but also led to a dose-dependent acceleration of the build-up as reflected in a significantly reduced latency to attain several exploratory landmarks. Finally, we tested the utility of the dimensionality emergence assay in assessing alterations in innate anxiety reported in mice carrying a knockout allele for the serotonin 1A receptor (Htr1a). Our findings support the validity of the dimensionality emergence assay as a method to extract an expanded repertoire of behavioral measures for the assessment of anxiety in laboratory mice.