Transgenik erkek farelerde hipotalamik paraventriküler oksitosin nöronlarının hipofrontalite üzerine etkileri

Oxytocin is a neuropeptide synthesized in the neurons of hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) and has a modulatory effect on various social behaviors. There is only one oxytocin receptor (OTR) known to date, and oxytocin exerts its neuromodulatory effects through this receptor. Oxytocin receptor is found in many areas of the brain, including the prefrontal cortex (PFC). In addition, several studies have shown that hypothalamic oxytocin neurons project to the PFC. Dopamine has an important role in regulating the cognitive function of the PFC and it is thought that oxytocin and dopamine systems work together and have similarities in the areas of organization and projection. In this study, it was aimed to investigate effects of oxytocin on hypofrontality-induced behavioral disturbances and the interaction of oxytocin and dopamine neurons in PFC. Adult male oxytocin-cre mice were used in this study. Recombinant adeno-associated virus with stimulatory hM3D subunit or inhibitory hM4D subunit were injected to paraventricular area in order to activate and inhibit oxytocin neurons. Then, effects of manipulation of oxytocin neurons on several behaviours were evaluated. Anxiety, locomotor activity, social interaction and short-term memory were examined by using elevated plus maze, open field test, social interaction test and T-maze test, respectively. Fiber photometry Ca2+ imaging was used to investigate interaction of oxytocin and dopamine neurons in the PFC. Oxytocin did not significantly change anxiety and locomotor activity. Inhibition of paraventricular oxytocin neurons significantly decreased the social novelty preference of oxytocin-cre mice and could cause short-term memory impairment. Further, Ca2+ signal recordings from prefrontal dopamine neurons were taken before and during acute activation of paraventricular oxytocin neurons, but no significant effect of acute activation of paraventricular oxytocin neurons on the activity of prefrontal dopamine neurons was found. In this study, the effects of manipulation of oxytocin neurons on various behaviors was revealed. Thus, modulation of prefrontal dopaminergic neuronal activity by chemogenetic activation and inhibition of oxytocin neurons was examined for the first time.