Functional ontogeny of hypothalamic Agrp neurons in neonatal mouse behaviors

Marcelo R. Zimmer, Antonio H.O. Fonseca, Onur Iyilikci, Rafael Dai Pra, Marcelo O. Dietrich



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 neu- rons showed a rapid increase in activity upon isola- tion 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 vo- calizations. Chemogenetic overactivation of these neurons further increased emission of these ultra- sonic vocalizations, but not milk ingestion. We uncovered important functional properties of hypo- thalamic Agrp neurons during mouse development, suggesting these neurons facilitate offspring-to- caregiver bonding.

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