Anatomical and functional characterization of fear-activated oxytocin neurons

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Oxytocin (OXT) is an evolutionarily ancient hypothalamic neuropeptide, which plays a crucial role in the neuroendocrine control of parturition and lactation in mammals. Beside these effects, OXT orchestrates various types of social behaviors, enhancing trust and attenuating fear. Recently, applying cell-type specific targeting of OXT neurons by recombinant adeno-associated virus (rAAV), we showed that OXT release from long-range axons in the central nucleus of amygdala suppresses freezing behavior in fear-conditioned rats. This finding raised a question on how endogenous OXT release is coordinated upon fear. We address this question in this project by employing rAAVs to express fluorescent markers or channel rhodopsin 2 in those OXT neurons, which start to express c-fos in response to fear. In the study we will pursue two goals: (1) To study – by employing recombinant viruses – the anatomical connections of “fear-sensitive” (i. e. cfos expressing) OXT neurons with the central amygdala and other forebrain structures controlling the fear response; 2) To study the functional significance of “fear-sensitive” OXT neurons by employing combined viral and optogenetic approaches in vitro and in vivo. In addition, this combination will be further applied together with the microdialysis technique to probe the bluelight evoked local release of OXT from axonal terminals in vivo.