Developmental effects of oxytocin neurons on social affiliation and processing of social information

Nunes, A.R., Gliksberg, M., Varela, S.A.M., Teles, M., Wircer, E., Blechman, J., Petri, G., Levkowitz, G., Oliveira, R.F.
The Journal of neuroscience : the official journal of the Society for Neuroscience   41(42): 8742-8760 (Journal)
Registered Authors
Blechman, Janna, Gliksberg, Michael, Levkowitz, Gil, Wircer, Einav
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Female
  • Male
  • Metronidazole/toxicity
  • Neurons/drug effects
  • Neurons/metabolism*
  • Oxytocin/antagonists & inhibitors*
  • Oxytocin/genetics
  • Oxytocin/metabolism*
  • Receptors, Oxytocin/antagonists & inhibitors
  • Receptors, Oxytocin/genetics
  • Receptors, Oxytocin/metabolism
  • Social Behavior*
  • Zebrafish
34470805 Full text @ J. Neurosci.
Hormones regulate behavior either through activational effects that facilitate the acute expression of specific behaviors or through organizational effects that shape the development of the nervous system thereby altering adult behavior. Much research has implicated the neuropeptide oxytocin (OXT) in acute modulation of various aspects of social behaviors across vertebrate species, and OXT signaling is associated with the developmental social deficits observed in autism spectrum disorders, however, little is known about the role of OXT in the neurodevelopment of the social brain. We show that perturbation of OXT neurons during early zebrafish development led to a loss of dopaminergic neurons, associated with visual processing and reward, and blunted the neuronal response to social stimuli in the adult brain. Ultimately, adult fish whose OXT neurons were ablated in early life, displayed altered functional connectivity within social decision-making brain nuclei both in naïve state and in response to social stimulus and became less social. We propose that OXT neurons have an organizational role, namely to shape forebrain neuroarchitecture during development and to acquire an affiliative response towards conspecifics.SIGNIFICANCE STATEMENTSocial behavior is developed over the lifetime of an organism and the neuropeptide oxytocin modulates social behaviors across vertebrate species, and is associated with neuro-developmental social deficits such as autism. However, whether oxytocin plays a role in the developmental maturation of neural systems that are necessary for social behavior remains poorly explored. We show that proper behavioral and neural response to social stimuli depends on a developmental process orchestrated by oxytocin neurons. Animals whose oxytocin system is ablated in early life show blunted neuronal and behavioral responses to social stimuli as well as wide ranging disruptions in the functional connectivity of the social brain. We provide a window into the mechanisms underlying oxytocin-dependent developmental processes that implement adult sociality.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes