Age-Related Differences in Emotional Behavior and Cognitive Function in Mice: Possible Role of Frontal Cortical-Hippocampal Functional Connectivity and Metabolomic Profiles

Abstract

AbstractDifferences in affective behaviors from early to late adulthood is thought to involve changes in frontal cortical responsiveness to negative valence stimuli. In mice, similar age-related changes in affective behaviors have been reported, but the functional neural circuitry remains unclear. In the present study, we investigated age variations in affective behaviors and functional connectivity in male and female C57BL6/J mice. Mice aged 10, 30 and 60 weeks (wo) were tested over 8 weeks for open field activity, sucrose preference, social interactions, fear conditioning, and functional neuroimaging. Frontal cortical and hippocampal tissues were excised for metabolomics analysis. Our results indicate that young 10wo mice display greater levels of anxiety-like locomotor behavior and develop robust fear conditioning compared to older adult and late middle-aged mice (30-60wo). This was accompanied by greater functional connectivity between a temporal cortical/auditory cortex network and subregions of the anterior cingulate cortex and ventral hippocampus, and a greater network modularity and assortative mixing of nodes in young versus older adult mice. Metabolome analyses identified differences in several essential amino acids between 10wo mice and the other age groups. The results support high ‘emotionality’ in younger versus older adult mice involving greater prefrontal-hippocampal connectivity.