Investigating the impact of sickness on the maternal brain and behavior

Project Summary / Abstract Maternal illness during the postpartum period introduces significant challenges to caregiving, with implications for both maternal and offspring survival. Postpartum sickness is linked to an increased risk of maternal anxiety, depression, impaired bonding, and breastfeeding deficits. However, the mechanisms by which sickness alters maternal neurobiology remain poorly understood. The paraventricular nucleus (PVN) of the hypothalamus is a critical regulator of maternal caregiving behaviors, housing neurons that synthesize and respond to neuropeptides such as oxytocin, vasopressin, and corticotropin-releasing hormone (CRH). This proposed research investigates how sickness disrupts PVN neuropeptidergic circuits to influence maternal caregiving. Using an acute inflammatory challenge induced by injection of the endotoxin lipopolysaccharide (LPS), I will examine caregiving behaviors in primiparous and multiparous mice. Preliminary behavioral analyses suggest that first-time mother mice exhibit reduced caregiving during sickness, increasing the risk of pup mortality. In contrast, experienced mother mice demonstrate behavioral adaptations that maintain caregiving under similar conditions. Preliminary in vivo photometry imaging of CRH activity suggests that PVN CRH neurons are highly active during sickness, as well as changes to PVN oxytocin neuron activity during nursing bouts. This proposal will test the hypothesis that neuroplasticity in PVN neuropeptide circuits during the postpartum period modulates caregiving behaviors under inflammatory stress. The proposed research has two aims: (1) to determine the effects of sickness on PVN neuropeptide circuit dynamics during caregiving and (2) to investigate how neuroplasticity in the PVN neuropeptidergic system promotes caregiving in experienced mothers despite illness. These findings will enhance our understanding of the neurobiological mechanisms underlying maternal caregiving and their resilience to physiological challenges, advancing knowledge relevant to maternal mental health and offspring survival.