SoSexOT - Deciphering Oxytocin Circuitries Orchestrating Socio-Sexual Behavior

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Reproduction is an essential feature of living organisms and is largely modulated in vertebrates by hypothalamic neuropeptide oxytocin (OT) and its homologs. In mammals, reproductive function is realized by complex socio-sexual (SS) behaviors, which can be mechanistically divided into precopulatory and copulatory behaviors, both modulated by OT. However, precise OT circuits underlying OT effects are far from clear. Although there are no doubts that OT promotes sexual behavior, the OT circuits orchestrating precopulatory behavior via forebrain regions are largely unknown. To address these questions, we will employ a recently developed genetic technique (called 'virus-based Genetic Activity-Induced Tagging' and abbreviated as vGAIT) to tag only those OT neurons which were activated during precopulatory and copulatory behaviors of rats. Using this technique, we will elucidate spatial distribution of such OT neurons in the hypothalamus, their phenotype and their projections as well as identify structures receiving input from tagged OT neurons in the forebrain, brainstem, and spinal cord. In parallel, in freely moving rats, we will record the activity of these OT neurons to elucidate their properties and excitability during SS behavior. Based on anatomical data, we will stimulate axonal OT release in those forebrain structures which are functionally related with SS behavior. At the end, using optogenetic and pharmacogenetic techniques, we will activate or inhibit entire populations of tagged OT neurons to monitor changes in SS behavior. The expected data will be entirely novel and will provide mechanistic insights into the physiology of the OT system in the context of SS behavior. Our proposal is highly relevant to human health as it will provide a basis for pathogenesis and possible pharmacological intervention in patients experiencing problems with sexual arousal and reproductive function.