Investigating the impact of sickness on the maternal brain and behavior

The National Institute of Child Health and Human Development awarded New York University $237,660 on January 1, 2026, under the Child Health and Human Development Extramural Research program (CFDA 93.865) to investigate how sickness disrupts maternal brain circuits and caregiving behavior during the postpartum period.

The research examines how acute inflammatory challenge—induced by lipopolysaccharide injection—alters neuropeptidergic circuits in the paraventricular nucleus of the hypothalamus, which regulates maternal caregiving. The study uses primiparous and multiparous mice to compare behavioral responses to sickness and to characterize changes in oxytocin, vasopressin, and corticotropin-releasing hormone neuron activity during nursing and caregiving. Preliminary findings indicate that first-time mother mice reduce caregiving during sickness, increasing pup mortality risk, while experienced mothers demonstrate behavioral adaptations that maintain caregiving despite illness. The proposal tests whether neuroplasticity in paraventricular nucleus neuropeptide circuits during the postpartum period modulates caregiving behaviors under inflammatory stress, with two primary aims: determining effects of sickness on neuropeptide circuit dynamics during caregiving, and investigating how neuroplasticity in experienced mothers promotes caregiving despite illness.

Performance occurs at New York University School of Medicine in New York, New York, with a period of performance from January 1, 2026, through August 31, 2028. This project grant is classified as an individual fellowship or training award.

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.