Examining the Impact of Social Isolation Stress in Adulthood on Avoidance Behavior and Hippocampal Plasticity in Mice with Partially Impaired CX3CR1 Signaling

Abstract

Social isolation stress in adulthood has profound relevance in society today, and individuals who have experienced this stress have shown greater susceptibility to psychiatric disorders related to emotional regulation. Past studies have explored multiple types of social stress at different timepoints, such in early life and adolescence, but it is currently unknown how social isolation stress in adulthood may impact behavior and neural connections in the hippocampus. The present study looked at how social isolation stress affected avoidance behavior, other EPM microbehaviors, neuronal outputs of inhibitory and excitatory neurons, and microglial changes in the ventral CA1 region. We investigated these measures in C57 wild type and Cx3cr1⁺/⁻ mice, in order to explore whether CX3CR1 signaling was necessary for social-isolation related changes. Firstly, we will discuss behavioral data or neural outputs that showed social isolation effects. The results demonstrated that 4 week social isolation conditions induced decreased avoidance behavior and increased PV intensity that was ameliorated by impaired CX3CR1 signaling. We also showed that social isolation weakened the correlations between EPM microbehaviors and quantitative metrics, and this observation was not mediated by CX3CR1 signaling. Our preliminary findings suggest that social isolation may downregulate GABAAδ receptor expression, and the potential role of CX3CR1 signaling remains to be studied. Next, we will discuss data that did not show differences due to social isolation. The EPM microbehaviors did not show alterations related to social isolation, but the stretch attend postures were different in Cx3cr1⁺/⁻ mice. The calbindin expression from active pyramidal cells in the ventral CA1 region were not different between housing conditions, but there was a genotypic difference. This study broadens our understanding of the effects of social isolation stress in adulthood on behavior and neuronal outputs in the ventral CA1, and whether CX3CR1 microglial-neuronal signaling is required for these changes.