Indra R. Bishnoi

One of the earliest and most important social bonds for many mammals is the bond formed with their mother. Mothers often provide essential benefits for offspring development and survival. Growing evidence suggests that this social bond is retained even when animals gain independence, such as during the juvenile period immediately following weaning. Here, we investigated whether or not juvenile mice (postnatal day [P]26) retain the ability to recognize and prefer their mothers post-weaning. We further investigated the strength of this bond using an acute immune activator. On P26, male and female C57BL/6J mice were intraperitoneally injected with the endotoxin lipopolysaccharide (LPS) or saline control (0.5 mg/kg). Four hours later, mice were subject to a five-chamber social preference task (the AGORA) containing their biological mother, a sex- and age-matched novel mouse, a sex- and age-matched sibling, a novel object, and an empty chamber. Our findings reveal that juvenile mice exhibit a strong maternal preference, which was significantly greater than chance and higher compared to any other social or non-social stimuli. While LPS exposure reduced the time spent investigating all stimuli, juvenile maternal preference was not significantly altered by LPS exposure. These effects were especially pronounced in females, while subtle shifts towards novel exploration began to emerge in males by P26. The novel multi-chamber task employed in the present study offered a more nuanced understanding of how social bonds evolve and vary across sex. The current findings suggest that juvenile mice have a robust social preference for their mother that is resilient to early-life immune activation.

Microglia are exceptionally dynamic resident innate immune cells within the central nervous system, existing on a continuum of morphologies and functions throughout their lifespan. They play vital roles in response to injuries and infections, clearing cellular debris, and maintaining neural homeostasis throughout development. Emerging research suggests that microglia are strongly influenced by biological factors, including sex, developmental stage, and their local environment. This review synthesizes findings on sex differences in microglial morphology and function in key brain regions, including the frontal cortex, hippocampus, amygdala, hypothalamus, basal ganglia, and cerebellum, across the lifespan. Where available, we examine how gonadal hormones influence these microglial characteristics. Additionally, we highlight the limitations of relying solely on morphology to infer function and underscore the need for comprehensive, multimodal approaches to guide future research. Ultimately, this review aims to advance the dialogue on these spatiotemporally heterogeneous cells and their implications for sex differences in brain function and vulnerability to neurological and psychiatric disorders.

Here we review the effects of immune activation primarily via lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, on hippocampal and non-hippocampal-dependent learning and memory. Rodent studies have found that LPS alters both the acquisition and consolidation of aversive learning and memory, such as those evoking evolutionarily adaptive responses like fear and disgust. The inhibitory effects of LPS on the acquisition and consolidation of contextual fear memory are discussed. LPS-induced alterations in the acquisition of taste and place-related conditioned disgust memory within bottle preference tasks and taste reactivity tests (taste-related), in addition to conditioned context avoidance tasks and the anticipatory nausea paradigm (place-related), are highlighted. Further, conditioned disgust memory consolidation may also be influenced by LPS-induced effects. Growing evidence suggests a central role of immune activation, especially pro-inflammatory cytokine activity, in eliciting the effects described here. Understanding how infection-induced immune activation alters learning and memory is increasingly important as bacterial and viral infections are found to present a risk of learning and memory impairment.

Risk-taking behaviors are a primary contributor to elevated adolescent injury and mortality. Locomotor and anxiety-like behaviors in rodents have been used to examine risk-taking. Here, we examined risk-taking behavior (i.e., changes in locomotor and anxiety-like behaviors) from early to late adolescence and adulthood in male and female rats in the open-field (OF) apparatus and the light–dark (LD) test. We also examined whether these behaviors are affected by an early adolescent immune stressor, lipopolysaccharide (LPS). Long-Evans male and female rats were injected with LPS (200 μg/kg) or vehicle control in early adolescence (postnatal day [PND] 30 and 32). Anxiety-like behavior and locomotor activity were measured in early (PND 38–40), late adolescence (PND 50), and adulthood (PND 88 and 98) in the OF and in early adolescence (PND 42) and adulthood (PND 90) in the LD test. Early and late adolescent rats displayed significantly greater locomotor and anxiety-like behaviors than adult rats in the OF and LD test. Sex differences were also found, with adolescent and adult females displaying greater locomotor and anxiety-like behaviors than male rats in the OF and LD tests. LPS administered two times in early adolescence did not have a significant impact on either locomotor or anxiety-like behaviors suggesting minimal impact of the immune stressor.