RESUMO
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.
Assuntos
Proteína Relacionada com Agouti/metabolismo , Comportamento Alimentar/fisiologia , Hipotálamo/citologia , Neurônios/metabolismo , Proteína Relacionada com Agouti/genética , Animais , Animais Recém-Nascidos , Ingestão de Alimentos/fisiologia , Comportamento Materno/fisiologia , Camundongos , Camundongos Knockout , Leite , Proteínas Proto-Oncogênicas c-fos/metabolismo , Isolamento Social , Comportamento de Sucção/fisiologia , Temperatura , Vocalização Animal/fisiologia , Ácido gama-Aminobutírico/metabolismoRESUMO
Hypothalamic Agrp neurons are critical regulators of food intake in adult mice. In addition to food intake, these neurons have been involved in other cognitive processes, such as the manifestation of stereotyped behaviors. Here, we evaluated the extent to which Agrp neurons modulate mouse behavior in spatial memory-related tasks. We found that activation of Agrp neurons did not affect spatial learning but altered behavioral flexibility using a modified version of the Barnes Maze task. Furthermore, using the Y-maze test to probe working memory, we found that chemogenetic activation of Agrp neurons reduced spontaneous alternation behavior mediated by the neuropeptide Y receptor-5 signaling. These findings suggest novel functional properties of Agrp neurons in memory-related cognitive processes.