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. 2019 Mar 8;13:30. doi: 10.3389/fnana.2019.00030

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Copyright © 2019 Haidar, Tin, Zhang, Nategh, Covita, Wykes, Rogers and Gundlach.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Putative circuits by which relaxin-3/RXFP3 signaling modulates activity in the hippocampus and medial septum/diagonal band of Broca. Simple schematic circuit diagram to illustrate how the relaxin-3/RXFP3 system is anatomically positioned to modulate the activity of the septohippocampal and hippocamposeptal systems, which are important for cognitive functions and related behaviors (Tsanov, 2015; Korotkova et al., 2018; Müller and Remy, 2018). Based on previous and current findings (see “Discussion” section), the ascending relaxin-3 projections from the NI innervate local and/or projection GABA/SST neurons in the mouse DG hilus (Haidar et al., 2017), and the GABA/PV+ve hippocampal projecting neurons and possibly other GABA interneurons (i.e., GABA/(PV−ve), as well as some glutamate neurons in the MS/DB, and modulate their activity via RXFP3 (current study; see e.g., Müller and Remy, 2018 for recent review). Existing data also indicates that neurons present in the other nodes of the septohippocampal system (SHS) are RXFP3-positive, but as their neurochemical identity is currently unknown, they are omitted for clarity. Furthermore, any possible collateralization of relaxin-3 neurons and all possible intra-MS/DB interconnections are not illustrated for clarity. Abbreviations: ACh, acetylcholine; CA1/CA3, CA1 and CA3 layers of hippocampus; DG hilus, dentate gyrus hilus; GABA, γ-aminobutyric acid; GCL, granule cell layer; Glut, glutamate; MS/DB, medial septum/diagonal band of Broca; NI, nucleus incertus; PV, parvalbumin; RLN3, relaxin-3; RXFP3, relaxin-family peptide receptor 3; SST, somatostatin; ±, plus or minus (PV).