Current Biology
Volume 28, Issue 7, 2 April 2018, Pages 1066-1078.e6
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Article
Oxytocin Signaling in the Lateral Septum Prevents Social Fear during Lactation

https://doi.org/10.1016/j.cub.2018.02.044Get rights and content
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Highlights

  • Lactating (Lac) mice do not express social fear

  • The OXT system in the LS is activated in Lac mice

  • Inhibition of OXT signaling in the LS of Lac mice reinstates social fear

  • Silencing of LS projecting OXT neurons blocks socialinvestigation in these mice

Summary

Oxytocin (OXT)-mediated behavioral responses to social and stressful cues have extensively been studied in male rodents. Here, we investigated the capacity of brain OXT receptor (OXTR) signaling in the lateral septum (LS) to prevent social fear expression in female mice using the social-fear-conditioning paradigm. Utilizing the activated OXT system during lactation, we show that lactating mice did not express fear 24 hr after social fear conditioning. Supporting the role of OXTR signaling in the LS in attenuation of social fear, synthetic OXT infusion or overexpression of OXTR in the LS diminished social fear expression, whereas constitutive OXTR knockout severely impaired social fear extinction in virgin mice. Subsequently, both pharmacological blockade of local OXTRs in the LS and chemogenetic silencing of supraoptic nucleus OXTergic afferents to the LS increased social fear expression in lactating mice. Hence, LS-projecting OXT neurons suppress social fear in female mice.

Keywords

chemogenetics
cued fear conditioning
GABA
hypothalamus
lactation
lateral septum
oxytocin receptor
paraventricular nucleus
supraoptic nucleus
social fear conditioning

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