Reward, Sociability, Affective Behavioral, and Functional Neuroimaging Differences in Young, Middle, and Aged C57BL/6J Male and Female Mice

Joy Buraima ’22

Student: Joy Buraima ’22
Research Mentors: Marcelo Febo and Marjory Pompilus (University of Florida College of Medicine: Department of Psychiatry McKnight Brain Institute)

Aging has several implications including deteriorating physical health and an increased risk for dementia, neuropsychiatric disorders and conditions that contribute to cognitive decline. That being said, aging is also associated with an increased incidence of mood disorders, which have been identified as a risk factor for the development of dementia. The goal of this pilot study was to establish a baseline model of normal aging in mice to identify what behavioral differences naturally occur in an aging population using behavioral tests and functional magnetic resonance.

According to the WHO, mental health conditions affect 15% of adults ages 60 and older and accounts for 6.6% of total disability. These conditions are often underdiagnosed because they occur along with other primary systemic and neurological conditions. More research on the neurobiological regulation of mood and affective states in aging subjects is thus needed. We investigated reward preferences, sociability, and anxiety-like behavior in male and female C57BL/6J mice tested after arrival at 10, 30, and 60 weeks of age. Mice were behavioral assessed using protocols for sucrose preference, social interaction/recognition, open field activity, and contextual fear condition (CFC). Mice were then imaged at 4.7 Tesla under combined dexmedetomidine/isoflurane anesthesia to measure resting state functional connectivity across cortical, striatal, hippocampal, and amygdala nodes. Initial analyses of general locomotor activity in an open field environment indicates that 10-week-old mice had higher levels of horizontal activity than 30- and 60-week-old mice. The total distance moved during testing showed a similar difference, however, stereotyped activity was not different between the 3 age groups. Interestingly, 10-week-old mice ambulated at much higher levels in the center of the test arena than 30- and 60-week-old mice. We used a 3-day CFC protocol that included a conditioning day, a retrieval day, and a 2nd retrieval day with changes to context. Mice in all age groups acquired tone-shock paired freezing behavior at the same rate and extent on day 1. All mice showed robust conditioned fear to tone alone on day 2, with 60-week-old mice trending towards higher levels of conditioned freezing relative to 10- and 30-week-old mice. On day 3, 10-week-old mice had lowest levels of conditioned freezing in a modified context. Our data suggest that aged (60-week-old) C57BL/6J mice are less active, exhibit anxiety-like behavior in an open field, and express higher levels of fear conditioning and more difficulty in suppressing conditioning in a modified context when compared to younger 10-week-old mice. Ongoing analyses will investigate reward preferences, sociability, and functional connectivity in these mice. The present preliminary results show initial evidence of differential expression of affective and cognitive behaviors in aged C57BL/6J mice.