Cognitive underpinnings of stress-induced skilled walking performance levels: The independent roles of memory and spatial orientation in mice

Stress exerts a profound yet complex influence on motor adaptation, with its effects on skilled walking performance mediated by cognitive and neurobiological factors. This study explored the impact of unpredictable chronic mild stress (UCMS) during adolescence on skilled walking performance in male and female Balb/cJ mice. The primary focus was on identifying memory and spatial orientation as potential predictors of motor resilience. A cohort of 133 mice was evaluated using the Ladder Rung Walking Test (LRWT) to assess motor proficiency, with skilled walking performance scores (SWPS) categorized as superior, regular, or inferior. Behavioral assessments, including the Barnes maze, Y-maze, open field, and elevated plus maze, were employed to evaluate cognitive and anxiety-like behaviors. Our findings revealed a nuanced interaction between stress and motor performance. Stress exposure did not directly predict skilled walking outcomes but elicited a dual effect: while some mice exhibited impaired motor performance, others showed enhancements, emphasizing the multifactorial nature of stress adaptation. Notably, primary latency in the Barnes maze emerged as a significant predictor of SWPS, with each additional second linked to a 2 % decrease in the likelihood of superior performance. This underscores the pivotal role of spatial orientation and memory in mediating motor adaptation under stress. Gene expression analyses of Bdnf exon IV, Drd1, and Drd2 in the sensorimotor cortex revealed no direct association with motor performance, suggesting that stress-related variability may involve complex molecular pathways. While no significant sex-based differences were observed, these findings highlight the need for integrative research addressing genetic, environmental, and neurobiological dimensions to fully elucidate stress-induced motor adaptations and inform interventions to mitigate motor deficits.