Coordinated regulation of feeding and social preferences by oxytocin in the rat and human

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The hypothalamic neuropeptide oxytocin (OT) is a crucial actor in the regulation of both social communication and feeding. However, it is largely unknown how one molecule – OT – can discriminately coordinate such distinct forms of behaviors. Based on accumulated reports that the insular cortex (IC) serves as the hub controlling both feeding and social behaviors, in our project we aim to investigate how OT signaling in the IC may form a preference towards food vs. conspecifics. To achieve this aim, we have built an international team in the framework of the DFG-Middle East program by experts in the functional anatomy of the OT system (Valery Grinevich, Mannheim), social behavior and in vivo electrophysiology (Shlomo Wagner, Haifa), and cellular/molecular biology of the IC (Kobi Rosenblum, Haifa). Using recently generated OT receptor (OTR) knock-in rats, we will implement an interdisciplinary approach to dissect (i) specific OTR circuits within the IC, (ii) investigate how OT modulates local networks in the IC, and (iii) study how evoked endogenous OT release within the IC contributes to goal-directed behavior, e.g., making a choice between two rewarding stimuli – food vs. conspecifics. In parallel, we will study the activity of the OT system and OTR neurons in the IC, using fiber photometry and extracellular recording in awake behaving rats, respectively. Next, applying cutting edge cellular and molecular techniques, including newly developed activity-dependent tagging of activated cells (termed CRAM), we will dissect intracellular pathways downstream of OTR, which are activate within IC neurons when the animal encounters innate or learned appetitive or aversive food sources or social experiences. Finally, we will study OTR expression and OTR intracellular signaling in cortical neurons differentiated from pluripotent stem cells from healthy adult male humans. Thus, in addition to gaining a novel information on functional diversity within the OT system, distinctly or concomitantly modulating social and feeding behaviors, our results will be highly translatable to human pathologies, such as Prader-Willi syndrome, characterized by joint alterations in social competence, feeding, and OT synthesis.