TY - JOUR T1 - Wiring diagram of the oxytocin system in the mouse brain JF - bioRxiv DO - 10.1101/2020.10.01.320978 SP - 2020.10.01.320978 AU - Seoyoung Son AU - Steffy B. Manjila AU - Kyra T. Newmaster AU - Yuan-ting Wu AU - Daniel J. Vanselow AU - Matt Ciarletta AU - Keith C. Cheng AU - Yongsoo Kim Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/10/01/2020.10.01.320978.abstract N2 - In the brain, oxytocin (OT) neurons make direct connections with discreet regions to regulate social behavior and diverse physiological responses. Obtaining an integrated neuroanatomical understanding of pleiotropic OT functions requires comprehensive wiring diagram of OT neurons. Here, we have created a whole-brain map of distribution and anatomical connections of hypothalamic OT neurons, and their relationship with OT receptor (OTR) expression. We used our brain-wide quantitative mapping at cellular resolution combined with a 2D flatmap to provide an intuitive understanding of the spatial arrangements of OT neurons. Then, we utilized knock-in Ot-Cre mice injected with Cre dependent retrograde monosynaptic rabies viruses and anterograde adeno associated virus to interrogate input-output patterns. We find that brain regions with cognitive functions such as the thalamus are reciprocally connected, while areas associated with physiological functions such as the hindbrain receive unidirectional outputs. Lastly, comparison between OT output and OTR expression showed no significant quantitative correlation, suggesting that OT transmission mostly occurs through indirect pathways. In summary, our OT wiring diagram provides structural and quantitative insights of distinct behavioral functions of OT neurons in the brain.Significance Statement Oxytocin (OT) neurons in the brain play an important role in socio-physiological responses. Impairment of OT signaling has been implicated in many neurodevelopmental disorders. To understand diverse OT functions in the context of discreet neural circuits, it is imperative to understand the anatomical arrangement of OT neurons across the whole brain in significant detail. Here, we have established a comprehensive brain-wide wiring diagram of OT neurons. Our anatomical and connectivity map of OT neurons includes brain-wide cell distribution, synaptic inputs, axonal outputs, and their relationships with the oxytocin receptor expression. This whole brain structural perspective of the OT system provides a foundation for understanding the diversity of neural circuits modulated by OT and will guide future circuit-based OT functional studies.Competing Interest StatementThe authors have declared no competing interest. ER -