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Here, we have used targeted recombination at the<jats:italic>Rln3<\/jats:italic>gene locus to generate an<jats:italic>Rln3<jats:sup>Cre<\/jats:sup><\/jats:italic>transgenic mouse line, and characterize the molecular identity and axonal projections of Rln3-expressing neurons. Expression of Cre recombinase in<jats:italic>Rln3<jats:sup>Cre<\/jats:sup><\/jats:italic>mice, and the expression of Cre-mediated reporters, accurately reflect the expression of Rln3 mRNA in all brain regions. In the NI, Rln3 mRNA is expressed in a subset of a larger population of tegmental neurons that express the neuropeptide neuromedin-b (NMB). These Rln3-expressing and NMB-expressing neurons also express the GABAergic marker GAD2 but not the glutamatergic marker Slc17a6 (VGluT2). Cre-mediated anterograde tracing with adeno-associated viruses (AAVs) shows that the efferents of the Rln3-expressing neurons in the DpMe and PAG are largely confined to the brain regions in which they originate, while the NI-Rln3 neurons form an extensive ascending system innervating the limbic cortex, septum, hippocampus, and hypothalamus. Viral anterograde tracing also reveals the potential synaptic targets of NI-Rln3 neurons in several brain regions, and the distinct projections of Rln3-expressing and non-expressing neurons in the pontine tegmentum. Rabies virus (RV)-mediated transsynaptic retrograde tracing demonstrates a probable synaptic link between NI-Rln3 neurons and GABAergic neurons in the septum, with implications for the modulation of neural activity in the septo-hippocampal system. Together, these results form the basis for functional studies of the NI-Rln3 system.<\/jats:p>","DOI":"10.1523\/eneuro.0272-20.2020","type":"journal-article","created":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T21:50:32Z","timestamp":1602712232000},"page":"ENEURO.0272-20.2020","source":"Crossref","is-referenced-by-count":21,"title":["Mapping Cell Types and Efferent Pathways in the Ascending Relaxin-3 System of the Nucleus Incertus"],"prefix":"10.1523","volume":"7","author":[{"given":"Nailyam","family":"Nasirova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lely 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