Conditioned fear memories that are context-specific shortly after conditioning generalize over time. We exposed rats to a context reminder 30 d after conditioning, which served to reinstate context-specificity, and investigated how this reminder alters retrieval-induced activity in the hippocampus and anterior cingulate cortex (aCC) relative to a no reminder condition. c-Fos expression in dorsal CA1 was observed following retrieval in the original context, but not in a novel context, whether or not the memory was reactivated, suggesting that dCA1 retains the context-specific representation. c-Fos was highly expressed in aCC following remote memory testing in both contexts, regardless of reminder condition, indicating that aCC develops generalized representations that are insensitive to memory reactivation.

Prolonged social isolation is associated with poor physical and mental health outcomes, findings observed in both humans, and rodent models of isolation. Humans, like mice, may engage in enhanced exploratory and social behaviour following isolation, which may protect against subsequent cognitive decline and psychological distress. Understanding how these effects may impact behaviour in older adults is particularly relevant, as this population is likely to experience periods of late-life social isolation. We report that late-life social isolation in female mice did not lead to robust depressive-like symptomology, altered social interaction behaviour, sensitivity to context fear acquisition and memory, or alterations in inflammatory cytokines (IL-6, IL-1β, Tnf-α) or microglial activation (Itgam) within the hippocampus. Rather, isolation increased hyperactivity and exploration behaviours. These findings have translational value as the first female mouse model of late-life social isolation, and provide evidence to inform the development of interventions aimed at promoting functional recovery following isolation in late-life.

Seizures induce brain region-dependent enhancements in microglia/macrophage activation. Neuronal subset–specific phosphatase and tensin homolog (PTEN) knockout (KO) mice display hyperactive mammalian target of rapamycin (mTOR) signaling in the hippocampus, cerebellum, and cortex followed by seizures that increase in severity with age. To determine if KO mice also exhibit alterations in the spatiotemporal activation pattern of microglia, we used flow cytometry to compare the percentage of major histocompatibility complex-II activated microglia/macrophages between KO and wildtype (WT) mice at 5, 10, and 15 weeks of age. At 5 weeks, microglia/macrophage activation was greater in the cortex, P < 0.001, cerebellum, P < 0.001, and hippocampus, P < 0.001, of KO compared to WT mice. At 10 weeks, activation was greatest in the cortex of KO mice, P < 0.001, in the cerebellum of WT mice, P < 0.001, but similar in the hippocampus, P > 0.05. By 15 weeks, activation in the hippocampus was more than 25 times greater in KO mice compared to WT mice, P < 0.001. We show that hyperactive mTOR signaling is associated with an altered spatiotemporal pattern of microglia/macrophage activation in the brain and induces an enhanced neuroimmune response in the hippocampus.

The likelihood of experiencing social isolation increases later in life, particularly for females. It remains unknown how late-life social isolation impacts cognition and affective behavior in aged mice. We assessed the impact of late-life social isolation in 18-month old female mice. One month of single-housing did not lead to robust depressive-like symptomology, altered social interaction behavior, or sensitivity to context fear acquisition or memory. Rather, isolation increased hyperactivity and exploration, and reduced anxiety-like behavior in the open field and elevated plus maze, findings that have been similarly observed in young female and male mice following early-life isolation. These findings suggest that hyperactivity is a robust behavior following social isolation across the lifespan.

No abstract