Behavioral Phenotyping Using Nonlinear Mixed Models for the Running Wheel

• Activity Number: 522 - Contributed Poster Presentations: Biometrics Section
• Type: Contributed
• Date/Time: Wednesday, July 31, 2019 : 10:30 AM to 12:20 PM
• Sponsor: Biometrics Section
• Author(s): Sandra McBride* and Gaylia Jean Harry, Ph.D. and Keith Shockley, Ph.D. and Helen Cunny, Ph.D.
• Companies: Social & Scientific Systems, Inc and National Institute of Environmental Health Sciences and National Institute of Environmental Health Sciences and National Institute of Environmental Health Sciences
• Keywords: nonlinear mixed effects models; running wheel; time series; circadian rhythm

Abstract

Screening for developmental neurotoxicity is an emerging priority for the National Toxicology Program. Modeling approaches are presented to characterize learning and memory in motor activity and to quantify known sexually dimorphic behavior. As a behavioral assessment, rodent activity on a running wheel has been used to describe long-term motor function and learning as well as circadian rhythm. Nonlinear mixed effects models are used to model acquisition and acclimation to the running wheel over the initial two weeks of exposure. These models parameterize learning differences for males and females and have advantages of parsimony and improved variance estimation over traditional repeated measures ANOVA. Nonlinear mixed effects models are also used to model onset and peak activity once behavior has stabilized. These models provide advantages over the common use of cosinor functions in the circadian rhythm literature which introduces bias in estimates of onset and peak by assuming symmetric waves of activity during the dark phase. Applications of these models allow quantification of sex differences in learning and diurnal activity of male and female mice.