Oxytocin-MCH circuit regulates monosynaptic inputs to MCH neurons and modulates social recognition memory

Abstract Oxytocin regulates social behaviors and has been linked to the etiology of autism and schizophrenia. Oxytocin and another hypothalamic neuropeptide, melanin concentrating hormone (MCH), share several physiological actions such as emotion, social behavior and recognition, maternal care, sexual behavior and stress, which suggests that these two systems may interact, however, how they would do it is not known. Here, we study the interactions between the oxytocin and MCH systems in behaviors related to autism and schizophrenia. Specifically, we examined the synaptic inputs of the oxytocin-to the MCH neurons. We selectively deleted oxytocin receptors (OXTR) from MCH neurons (OXTR-cKO mice) using a Cre/loxP recombinase-technology, and used rabies-mediated circuit mapping technique to reveal the changes in the direct monosynaptic inputs to MCH neurons. We examined the behavioral responses of OXTR-cKO mice. Deletion of OXTR from MCH neurons induced a significant decrease in the primary inputs received by MCH neurons from the paraventricular nucleus and the lateral hypothalamus, and from the nucleus accumbens and ventral tegmental area. While OXTR-cKO mice exhibited similar social interactions as control mice, they displayed significantly impaired social recognition memory and increased stereotypic behavior. Our study identifies a selective role for the oxytocin-MCH pathway in social recognition memory and stereotyped behavior that are relevant to psychiatric disorders such as schizophrenia and autism, and warrant further investigation of this circuit to uncover potential benefit of targeting the oxytocin-MCH circuit as a novel therapeutic target for treatment of social recognition deficits in these two disorders.