Oxytocin-ergic Control of Social Anxiety: An Interplay between Periaqueductal Gray and Central Amygdala

• Applicant: Dr. Quirin Krabichler
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Experimental and Theoretical Network Neuroscience
• Term: from 2021 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 459051339

The hypothalamic neuropeptide oxytocin (OT) is well-known for its crucial role in the modulation of various forms of social behaviours, including social anxiety. Anxiolytic effects of OT are realized via its action on the central nucleus of amygdala (CeA), however other brain regions are also involved. In my project, I will primarily focus on the OT signalling within the periaqueductal gray (PAG), which contains neurons expressing OT receptors (OTR) and is known to be involved in the neural control of social behaviours as well as anxiety. Furthermore, the PAG is tightly interconnected with the CeA. Based on this evidence, I hypothesize that the social anxiety is modulated by the OTR neurons in the PAG and is further tuned via an interplay between the OT>>PAG and OT>>CeA pathways. To test these hypotheses, I will work in a highly social animal model, the rat, and perform the following experiments: First, I will analyse the neuroanatomy and connectivity of the OT>>PAG circuit, using a recently generated OTR-IRES-Cre rat line in combination with recombinant viral vectors. Second, I will employ an activity-dependent genetic tagging technique to reveal the patterns of PAG OTR neurons activated during social anxiety episodes. Third, I will simultaneously record in vivo the natural activity of OTR cells in the PAG and CeA during anxiety episodes, applying fiber photometry in OTR-IRES-Cre rats. Finally, I will apply optogenetics and pharmacology to concomitantly or separately manipulate the activity of OT>>PAG and OT>>CeA pathways to investigate their roles in social anxiety behaviour. Altogether, my study will provide novel information on OT-dependent mechanisms of modulation of social anxiety and may thus pave the way towards targeted treatments of patients afflicted with socio-emotional disorders.

• DFG Programme: WBP Position