Experience-dependent regulation of social and parental behaviors by the oxytocin receptor-expressing neurons in the medial preoptic area

• Applicant: David Keller, Ph.D.
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 551841466

Social behaviors, either cooperative or parental, are crucial for the survival and reproduction. Impairment in social behaviors accompanies a range of neuropsychiatric disorders, such as postpartum depression, major depression, and autism spectrum disorders. Despite the obvious importance of social and parental behaviors, neural circuit mechanisms underlying the regulation of these behaviors remain largely elusive. The role of medial preoptic area (MPOA) in the control of parental behaviors, mating behaviors, aggression, predatory hunting, regulation of body temperature, and sleep-wakefulness is well-established. We know that the lesion of MPOA disrupts parental behavior in both male and female mice. Furthermore, MPOA's role in intermale and interfemale social behaviors (hereafter referred to as social behaviors) has also been established. Despite the important role of the MPOA in regulating both parental and social behaviors, the exact mechanism of balancing between these two behavioral forms remains to be elucidated. The role of oxytocin and oxytocin receptor (OxtR)-expressing cells in both social and parental behaviors has been established. The MPOA comprises several neurochemically defined neuronal groups including OxtR cells. It has been demonstrated that the expression of the OxtR is dimorphic in the MPOA, and its expression is significantly greater in female than in male mice. Microinjection of oxytocin into the MPOA has been shown to facilitate copulation in male rats, and this copulation stimulation also increased OxtR mRNA expression. Combining optogenetics and calcium imaging in transgenic behaving mice, I will pursue 3 complementary aims that integrate different crucial aspects of neuronal dynamics underlying parental and social behaviors: (1) Characterize spontaneous population dynamics of oxytocin receptor (OxtR)-expressing cells in the medial preoptic area (OxtR-MPOA) and define how they encode specific phases of social, mating and parental behaviors at multiple time scales (as virgin animals, as sexually experienced animals and as parents) in both male and female animals; (2) Unravel a causal role of OxtR-expressing cells in the MPOA in regulation of social and parental behaviors in both virgin male and female mice, as well as in parents. Taken together, we hypothesize that the OxtR-expressing cells of the MPOA play a significant role in balancing between social and parental behaviors in both male and female. This study will characterize neuronal circuits regulating social and parental behaviors and will advance our understanding of neuronal mechanisms underlying behavioral choices.

• DFG Programme: WBP Position