Gestational immune activation disrupts hypothalamic neurocircuits of maternal care behavior

• Published in: Molecular psychiatry Vol. 29; no. 4; pp. 859 - 873
• Main Authors: Zambon, Alice, Rico, Laura Cuenca, Herman, Mathieu, Gundacker, Anna, Telalovic, Amina, Hartenberger, Lisa-Marie, Kuehn, Rebekka, Romanov, Roman A., Hussaini, S. Abid, Harkany, Tibor, Pollak, Daniela D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2024; Nature Publishing Group
• Subjects: 14/32; 42/44; 631/378; 64/110; 64/60; 692/699/476; Animals; Behavior; Behavior, Animal - physiology; Behavioral Sciences; Biological Psychology; Brain; Dopamine receptors; Dopaminergic Neurons - metabolism; Experiments; Exploratory behavior; Exploratory Behavior - physiology; Female; Females; Galanin; Galanin - metabolism; Hypothalamus; Hypothalamus - metabolism; Immune response; Immunogenicity; Infections; Male; Maternal behavior; Maternal Behavior - physiology; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Morphology; Neurons; Neurons - metabolism; Neurosciences; Parental behavior; Pharmacotherapy; Physiology; Poly I-C - pharmacology; Polyinosinic:polycytidylic acid; Pregnancy; Pregnancy complications; Prenatal Exposure Delayed Effects - immunology; Preoptic area; Preoptic area (medial); Preoptic Area - metabolism; Psychiatry; Ventral Tegmental Area - immunology; Ventral tegmentum; Viral infections; Viruses
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/s41380-022-01602-x

Immune activation is one of the most common complications during pregnancy, predominantly evoked by viral infections. Nevertheless, how immune activation affects mother–offspring relationships postpartum remains unknown. Here, by using the polyinosinic-polycytidylic acid (Poly I:C) model of gestational infection we show that viral-like immune activation at mid-gestation persistently changes hypothalamic neurocircuit parameters in mouse dams and, consequently, is adverse to parenting behavior. Poly I:C-exposed dams favor non-pup-directed exploratory behavior at the expense of pup retrieval. These behavioral deficits are underlain by dendrite pruning and lesser immediate early gene activation in Galanin (Gal) + neurons with dam-specific transcriptional signatures that reside in the medial preoptic area (mPOA). Reduced activation of an exclusively inhibitory contingent of these distal-projecting Gal + neurons allows for increased feed-forward inhibition onto putative dopaminergic neurons in the ventral tegmental area (VTA) in Poly I:C-exposed dams. Notably, destabilized VTA output specifically accompanies post-pup retrieval epochs. We suggest that gestational immunogenic insults bias both threat processing and reward perception, manifesting as disfavored infant caregiving.