Home-Cage Monitoring Methods Reveal Age- and Strain-Related Differences in Motor, Thermal, and Cognitive Functions in Male Mice of Two Inbred Strains

Aging is associated with cognitive decline and behavioral alterations linked to neurobiological changes. Rodent models are crucial for investigating age-related variations in cognitive flexibility, anxiety, and circadian rhythms. Comparing two inbred strains, C57BL/6 J and 129S2/SvPasCrl, helps clarify how genetic background influences these aging-related outcomes. Advanced RFID-based automated home-cage platforms (Mouse Matrix and IntelliCage) were utilized to quantify circadian locomotor activity, core body temperature dynamics, and cognitive performance in group-housed mice. These systems enable continuous, high-resolution monitoring of behavioral and physiological data within an automated, ethologically relevant environment. Significant age- and strain-dependent differences were observed in temperature rhythms, locomotor activity, anxiety-like behavior, and adaptability to environmental changes. Aged mice showed reduced activity and impaired anticipatory behavior, indicating disrupted circadian regulation. The 129S2/SvPasCrl strain displayed higher anxiety and slower adaptation, whereas C57BL/6 J mice exhibited greater cognitive flexibility and more rapid learning. Conventional behavioral tests performed outside the home-cage, such as open field or maze-based tasks, rely on brief, experimenter-dependent sessions that may introduce handling stress and novelty effects. In contrast, MM and IC provide continuous, unbiased assessment within the familiar home-cage environment, reducing stress and improving ecological validity. Advanced home-cage monitoring systems offer reliable platforms for detecting strain- and age-specific behavioral and physiological differences. These findings highlight the importance of automated, naturalistic approaches for improving reproducibility and translational relevance in aging and neuropsychiatric research. • Home-cage monitoring methods uncover age- and strain-dependent behavioral phenotypes. • Aging attenuates circadian thermoregulation and anticipatory motor responses. • C57BL/6 J male mice exhibit enhanced adaptability after environmental changes compared with 129SV. • 129SV male strain shows higher thermal stability but reduced activity. • Automated RFID-based innovative techniques enable unbiased, ethologically valid phenotyping.