Automatically annotated motion tracking identifies a distinct social behavioral profile following chronic social defeat stress

Abstract

Severe stress exposure is a global problem with long-lasting negative behavioral and physiological consequences, which increases the risk of stress-related disorders such as major depressive disorder (MDD). An essential characteristic of MDD is the impairment of social functioning and lack of social motivation. Chronic social defeat stress is an established animal model for MDD research, which induces a cascade of physiological and social behavioral changes. The current developments of markerless pose estimation tools allow for more complex and socially relevant behavioral tests, but the application of these tools to social behavior remains to be explored. Here, we introduce the open-source tool DeepOF to investigate the individual and social behavioral profile in mice by providing supervised and unsupervised pipelines using DeepLabCut-annotated pose estimation data. The supervised pipeline relies on pre-trained classifiers to detect defined traits for both single and dyadic animal behaviors. Subsequently, the unsupervised pipeline explores the behavioral repertoire of the animals without label priming, which has the potential of pointing towards previously unrecognized motion motifs that are systematically different across conditions. We here provide evidence that the DeepOF supervised and unsupervised pipelines detect a distinct stress-induced social behavioral pattern, which was particularly observed at the beginning of a novel social encounter. The stress-induced social behavior shows a state of arousal that fades with time due to habituation. In addition, while the classical social avoidance task does identify the stress-induced social behavioral differences, both DeepOF behavioral pipelines provide a clearer and more detailed profile. DeepOF aims to facilitate reproducibility and unification of behavioral classification of social behavior by providing an open-source tool, which can significantly advance the study of rodent individual and social behavior, thereby enabling novel biological insights and subsequent drug development for psychiatric disorders.

A behavioral roadmap for the development of agency in the rodent

“…We employed machine vision tools and developed methods for quantifying a set of unique developmental trajectories. Rodent families have been studied both in natural environments to establish ground truth measurements (Ågren 1984;Ostermeyer & Elwood 1984;Hurtado-Parrado et al 2015), and in simplified laboratory enclosures to conduct mechanistic experiments (Lahvis 2017;Bordes et al 2023). Laboratory studies generally exploit brief, stereotyped behaviors in which one or two subjects are tested in a foreign environment.…”

“…This period of significant development -from complete dependency on the mother until ~P15 to complete independence by P30-P40 -should contain a large array of complex behavior interactions, yet the interaction of individual behaviors is uncertain. Critically, characterizing all the behavioral stages and neural mechanisms that yield independent animals with full agency -requires an approach that combines the advantages of field studies with the precise identity and subsecond precision tracking available during transient lab observations (Lin & Wilbrecht 2022;Bordes et al 2023).…”

Spared nerve injury decreases motivation in long-access homecage-based operant tasks in mice

“…Prior work has demonstrated that integrating performance across various behavioral assays can lead to more sensitive and reliable measures of the overall socalled "emotionality" of preclinical rodent models. 9,13,38,90 Whether this same approach would apply for injury-induced negative affect is unclear. To determine whether a normalized "emotionality" behavioral z-score could reflect chronic neuropathic injury, we next tested this concept by normalizing each individual output from a single behavioral assay (eg, % time in center and distance travelled in the open field; Table 1) into a single assay score.…”

Neuropathic injury drives a generalized negative affective state in mice

“…The exception to that was in the more challenging operant tasks (i.e., FR3 and PR; Figures 6-9). Prior work has demonstrated that integrating performance across various behavioral assays can lead to more sensitive and reliable measures of the overall so-called 'emotionality' of preclinical rodent models [9,12,35,78]. Whether this same approach would apply for injury-induced negative affect is unclear.…”