NON-CANONICAL SIGNALLING FUNCTION OF OXYTOCIN CELLS IN SOCIAL BEHAVIOUR CONTROL

As social creatures, we are impacted by the mere presence of our conspecifics. Behavioural adaptations, such as an increased drive for social exploration following isolation, have been linked to circuit changes involving oxytocin signalling, but the underlying molecular and cellular mechanisms are not fully understood. Previous work demonstrated instances of glutamate release from oxytocinergic axons, but its prevalence, target cells, plasticity and functional importance remain to be explored. In this study, we used genetic and viral tracing approaches to probe glutamate release from oxytocinergic axons derived from the paraventricular nucleus (PVN) of juvenile mice. Using genetic marking and fluorescent in situ hybridisation, we found that essentially all oxytocinergic cells in the PVN arise from a glutamatergic lineage, with most maintaining substantial expression levels of the vesicular glutamate transporter Vglut2 at P28. Remarkably, conditional knockout of Vglut2 in oxytocinergic cells substantially reduced social interactions in social recognition assays - despite normal numbers of oxytocin cells with unaltered intrinsic properties in the PVN. To identify candidate downstream targets of glutamatergic transmission, we used virus-based anterograde tracing. This approach identified parvalbumin-positive interneurons and pyramidal cells in CA2, a region with crucial functions in social recognition memory. In ongoing work, we are combining a trans-synaptic labelling tool that specifically marks cells connected through AMPA-type glutamate receptor-containing synapses (ATLAS). Moreover, we are interrogating plasticity of oxytocin and glutamate co-release during behavioural states such as social isolation and reunion.