Inhibition of oxytocin neurons during key periods of development has long-term behavioral and body composition effects
Abstract
Background Oxytocin (OT) is a key neuromodulator of social behavior in mammals, and accumulating evidence supports the existence of a critical period for OT action during infancy. However, other developmental windows remain poorly explored, and it remains unclear whether OT exert distinct functions depending on the timing of its activity. In this study, we aimed to determine whether specific developmental stages exist during which OT-expressing neurons play a decisive role with long-term consequences. Methods We used a chemogenetic approach to transiently inhibit OT-expressing neurons during three postnatal developmental periods: infancy, the juvenile period, and young adulthood in male and female mice. Behavioral and metabolic outcomes were then assessed longitudinally. We also examined the effects of inhibiting OT neurons during late fetal stages and at birth. Results Social memory was consistently impaired in males, regardless of the timing of neuronal inactivation. The most pronounced behavioral effects were observed following inhibition during infancy in both sexes. Metabolically, adult males from all cohorts exhibited increased body weight, whereas increased fat mass and adipocyte size hypertrophy were specifically observed following inhibition during the juvenile period. Notably, inhibition of OT-expressing neurons around the time of birth resulted in delayed parturition and altered neonatal feeding behavior. Limitations OT-expressing neurons release multiple signaling molecules. However, converging evidence suggests that the observed phenotypes are primarily attributable to OT deficiency. Although this study demonstrates long-term behavioral and metabolic consequences of transient OT neuron inhibition, further experiments are required to elucidate underlying mechanisms and identify additional effects. Conclusions Transient inhibition of OT-expressing neurons during distinct postnatal developmental periods leads to long-lasting effects on social behavior and metabolism, with outcomes depending on both the timing of inhibition and sex. Furthermore, our findings reveal an unexpected role for fetal/neonatal OT neurons in regulating the timing of birth and early feeding behavior.
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BibTeX
@article{schaller2026inhibition,
title = {{Inhibition of oxytocin neurons during key periods of development has long-term behavioral and body composition effects}},
author = {Fabienne Schaller and Marie-Sophie Alifrangis and Pierre-Yves Barelle and Catarina Santos and Roman Tyzio and Alessandra Bertoni and Felix Omnes and Yasmine Belaidouni and Francesca Bader and Emilie Pallesi-Pocachard and Jean-Luc Gaiarsa and Sebastien Bouret and Françoise Muscatelli},
journal = {Molecular Autism},
year = {2026},
month = sep,
doi = {10.1186/s13229-026-00744-x},
url = {https://hal.science/hal-05795636v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Inhibition of oxytocin neurons during key periods of development has long-term behavioral and body composition effects
AU - Fabienne Schaller
AU - Marie-Sophie Alifrangis
AU - Pierre-Yves Barelle
AU - Catarina Santos
AU - Roman Tyzio
AU - Alessandra Bertoni
AU - Felix Omnes
AU - Yasmine Belaidouni
AU - Francesca Bader
AU - Emilie Pallesi-Pocachard
AU - Jean-Luc Gaiarsa
AU - Sebastien Bouret
AU - Françoise Muscatelli
PY - 2026
DA - 2026/09/09
JO - Molecular Autism
DO - 10.1186/s13229-026-00744-x
UR - https://hal.science/hal-05795636v1
AB - Background Oxytocin (OT) is a key neuromodulator of social behavior in mammals, and accumulating evidence supports the existence of a critical period for OT action during infancy. However, other developmental windows remain poorly explored, and it remains unclear whether OT exert distinct functions depending on the timing of its activity. In this study, we aimed to determine whether specific developmental stages exist during which OT-expressing neurons play a decisive role with long-term consequences. Methods We used a chemogenetic approach to transiently inhibit OT-expressing neurons during three postnatal developmental periods: infancy, the juvenile period, and young adulthood in male and female mice. Behavioral and metabolic outcomes were then assessed longitudinally. We also examined the effects of inhibiting OT neurons during late fetal stages and at birth. Results Social memory was consistently impaired in males, regardless of the timing of neuronal inactivation. The most pronounced behavioral effects were observed following inhibition during infancy in both sexes. Metabolically, adult males from all cohorts exhibited increased body weight, whereas increased fat mass and adipocyte size hypertrophy were specifically observed following inhibition during the juvenile period. Notably, inhibition of OT-expressing neurons around the time of birth resulted in delayed parturition and altered neonatal feeding behavior. Limitations OT-expressing neurons release multiple signaling molecules. However, converging evidence suggests that the observed phenotypes are primarily attributable to OT deficiency. Although this study demonstrates long-term behavioral and metabolic consequences of transient OT neuron inhibition, further experiments are required to elucidate underlying mechanisms and identify additional effects. Conclusions Transient inhibition of OT-expressing neurons during distinct postnatal developmental periods leads to long-lasting effects on social behavior and metabolism, with outcomes depending on both the timing of inhibition and sex. Furthermore, our findings reveal an unexpected role for fetal/neonatal OT neurons in regulating the timing of birth and early feeding behavior.
SN - 2040-2392
ER -