Functional Ontogeny of Hypothalamic Agrp Neurons in Neonatal Mouse Behaviors

Cell. 2019 Jun 27;178(1):44-59.e7. doi: 10.1016/j.cell.2019.04.026. | PubMed

Marcelo R Zimmer¹, Antonio H O Fonseca², Onur Iyilikci³, Rafael Dai Pra¹, Marcelo O Dietrich⁴

1. Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Graduate Program in Biological Sciences-Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035, Brazil.
2. Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Graduate Program in Microelectronics, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 15064, Brazil.
3. Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
4. Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA; Graduate Program in Biological Sciences-Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035, Brazil. Electronic address: marcelo.dietrich@yale.edu.

Abstract

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.

Presented By Marcelo Zimmer