Do behavioral test scores represent repeatable phenotypes of female mice?

The marble bury test is a commonly applied behavioral test often used to screen pharmaceuticals for treatment of compulsivity or anxiety disorders and to better understand the underlying neurobiology of these conditions using rodent models. We explore the use of the marble bury test in a repeated fashion over longer time intervals to assess how it may be used in a more chronic context. Assuming that marble bury scores represent a neurobiological phenotype of an individual, we hypothesize that the measurement of this phenotype is repeatable over time in a healthy animal. We performed four trials over the course of 12 weeks, using three overlapping scores for marble burying: 100%, >50%, and >0% buried. Despite intertrial differences in the mean number of marbles buried, we found significant repeatability scores across 12 weeks for two measurements: marbles buried 100% and marbles buried >50%. Exploration of pairwise repeatabilities between the trials revealed highest repeatability during shorter time intervals. Although the effect of time is difficult to disentangle from possible effects of body size/development on the scores, we hypothesize that a combination of these two factors together influence repeatability of scores and should be explored further. Understanding the patterns in repeatability in marble burying scores can inform experimental design to use this test over longer time intervals for chronic conditions or long-term interventions. Additionally, these data indicate that a pre-test, post-test design is possible, which can reduce the number of animals needed for research applications while maintaining statistical power.

Contributions of Distinct Auditory Cortical Inhibitory Neuron Types to the Detection of Sounds in Background Noise.

The ability to separate background noise from relevant acoustic signals is essential for appropriate sound-driven behavior in natural environments. Examples of this separation are apparent in the auditory system, where neural responses to behaviorally relevant stimuli become increasingly noise invariant along the ascending auditory pathway. However, the mechanisms that underlie this reduction in responses to background noise are not well understood. To address this gap in knowledge, we first evaluated the effects of auditory cortical inactivation on mice of both sexes trained to perform a simple auditory signal-in-noise detection task and found that outputs from the auditory cortex are important for the detection of auditory stimuli in noisy environments. Next, we evaluated the contributions of the two most common cortical inhibitory cell types, parvalbumin-expressing (PV+) and somatostatin-expressing (SOM+) interneurons, to the perception of masked auditory stimuli. We found that inactivation of either PV+ or SOM+ cells resulted in a reduction in the ability of mice to determine the presence of auditory stimuli masked by noise. These results indicate that a disruption of auditory cortical network dynamics by either of these two types of inhibitory cells is sufficient to impair the ability to separate acoustic signals from noise.