Functional Ontogeny of Hypothalamic Agrp Neurons in Neonatal Mouse Behaviors

Hypothalamic Agrp neurons regulate food ingestion in adult mice. Whether these neurons are functional before animals start to ingest food is unknown. Here, we studied the functional ontogeny of Agrp neurons during breastfeeding using postnatal day 10 mice. In contrast to adult mice, we show that isolation from the nursing nest, not milk deprivation or ingestion, activated Agrp neurons. Non-nutritive suckling and warm temperatures blunted this effect. Using in vivo fiber photometry, neonatal Agrp neurons showed a rapid increase in activity upon isolation from the nest, an effect rapidly diminished following reunion with littermates. Neonates unable to release GABA from Agrp neurons expressed blunted emission of isolation-induced ultrasonic vocalizations. Chemogenetic overactivation of these neurons further increased emission of these ultrasonic vocalizations, but not milk ingestion. We uncovered important functional properties of hypothalamic Agrp neurons during mouse development, suggesting these neurons facilitate offspring-to-caregiver bonding. [Display omitted] •Isolation from the nest activates Agrp neurons in neonatal mice•Care and warmth, but not milk, blunts activation of Agrp neurons•Neonatal Agrp neurons modulate isolation-induced ultrasonic vocalizations•Agrp neurons increase milk ingestion in 15- but not in 10-day-old mice Hypothalamic Agrp neurons play a role in offspring-to-caregiver bonding independent of their role in food ingestion.