P.1.012 - Inhibition of miR-132 impairs extinction of social fear in mice: Possible involvement in oxytocin receptor signalling

Abstract

Neuronal microRNAs are important post-transcriptional regulators of gene expression. For example, miR-132 plays a major role in neuronal plasticity and development, suggesting its crucial function in the regulation of various genes associated with anxiety disorders. Another example is miR-124, which is known to regulate social behaviour in mice and humans via AMPA receptor subunit expression [1]. Recently, we developed a social fear conditioning (SFC) paradigm, a mouse model that resembles social anxiety disorder in humans. Here, the prosocial neuropeptide oxytocin (OXT) has been shown to reverse social fear when administered intracerebroventricularly (icv) or local into the lateral septum (LS) of male mice. Additionally, OXT is released within the LS during extinction training in unconditioned mice [2]. Moreover, we showed recently that icv OXT leads to an increased miR-132 level within the paraventricular nucleus of the rat hypothalamus in a sex-independent manner, suggesting a possible involvement of this particular microRNA in OXT receptor (OXTR) signalling. Since the underlying molecular mechanisms of OXTR signalling in the context of its social fear reversing properties are not well studied, we examined the involvement of microRNAs in extinction of SFC induced social fear in male mice. 90 min after acquisition of SFC, miR-132 and miR-124 levels in the LS of conditioned (SFC+) mice are elevated compared to unconditioned (SFC-) mice (both p