Oxytocin signaling in the ventral hippocampus: from modulation of the local circuit to socio-sexual behavior

• Applicant: Professor Dr. Valery Grinevich
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 433153533

• Final Report Year: 2023

Final Report Abstract

In the course of our work we analyzed the OT-ergic innervation of the vHipp and demonstrated that both the PVN and SON ubuquitosly project to this region, supporting and exploring our initial tracing studies. Further, we identified three OTR+ cell types in the vHipp CA1, INs, OTR+ pyramids and RGCs. Recently developed retro FLP/FRT technique helped us to demonstrate that these two types of cells are largerly projecting to olfactory regions and thus allowed us to initiate behavioral experiments, which aim to precisely dissect the role of OTR+ principle cells in the modulation of odor-driven sexual information. At the present stage of the work, we clearly demonstrated that activation of all OTR+ vHipp cells or – most fascinating – exclusively OTR+ INs increased male rats´ interest in urine of mating parterns. This suggests that the OT-sensitive circuit within the vHipp may represent a potential substrate of monogamic behavior known for a very limited number of mammalian species. However, the preference towards the partner female urine, which we observed in the FEUD test was diminished in actual social interaction paradigm, which can be explained by the activation of additional sensory inputs, as well as activation of the distinct circuits, which prevent monogamic behavior in favor of polygamy to facilitate a propagation of mammalian species in natural habitat. In conclusion, the overarching goal of this project, even lasting beyond the funding period, remains to validate our hypothesis that OT signaling in the vHippo is an evolutionary old mechanism of monogamy hidden in the mammalian brain.

Publications

• Distinct dynamics of social motivation drive differential social behavior in laboratory rat and mouse strains. Nature Communications, 11(1).
  Netser, Shai; Meyer, Ana; Magalnik, Hen; Zylbertal, Asaph; de la Zerda, Shani Haskal; Briller, Mayan; Bizer, Alexander; Grinevich, Valery & Wagner, Shlomo
  
• Astrocytes mediate the effect of oxytocin in the central amygdala on neuronal activity and affective states in rodents. Nature Neuroscience, 24(4), 529-541.
  Wahis, Jérôme; Baudon, Angel; Althammer, Ferdinand; Kerspern, Damien; Goyon, Stéphanie; Hagiwara, Daisuke; Lefevre, Arthur; Barteczko, Lara; Boury-Jamot, Benjamin; Bellanger, Benjamin; Abatis, Marios; Da, Silva Gouveia Miriam; Benusiglio, Diego; Eliava, Marina; Rozov, Andrei; Weinsanto, Ivan; Knobloch-Bollmann, Hanna Sophie; Kirchner, Matthew K.; Roy, Ranjan K. ... & Charlet, Alexandre
  
• Efficiency of cell-type specific and generic promoters in transducing oxytocin neurons and monitoring their neural activity during lactation. Scientific Reports, 11(1).
  Thirtamara, Rajamani Keerthi; Leithead, Amanda B.; Kim, Michelle; Barbier, Marie; Peruggia, Michael; Niblo, Kristi; Barteczko, Lara; Lefevre, Arthur; Grinevich, Valery & Harony-Nicolas, Hala
  
• Neuroanatomical and Functional Relationship Between Parvocellular and Magnocellular Oxytocin and Vasopressin Neurons. Masterclass in Neuroendocrinology, 149-165. Springer International Publishing.
  Althammer, Ferdinand; Stern, Javier E. & Grinevich, Valery
  
• Oxytocin and vasopressin within the ventral and dorsal lateral septum modulate aggression in female rats. Nature Communications, 12(1).
  Oliveira, Vinícius Elias de Moura; Lukas, Michael; Wolf, Hannah Nora; Durante, Elisa; Lorenz, Alexandra; Mayer, Anna-Lena; Bludau, Anna; Bosch, Oliver J.; Grinevich, Valery; Egger, Veronica; de Jong Trynke, R. & Neumann, Inga D.
  
• The Human Hypothalamus - Middle and Posterior Region. (2021). Handbook of Clinical Neurology.
  Althammer, F.; Eliava, M. & Grinevich, V.
  
• A thalamo-preoptic pathway promotes social grooming in rodents. Current Biology, 32(21), 4593-4606.e8.
  Keller, Dávid; Láng, Tamás; Cservenák, Melinda; Puska, Gina; Barna, János; Csillag, Veronika; Farkas, Imre; Zelena, Dóra; Dóra, Fanni; Küppers, Stephanie; Barteczko, Lara; Usdin, Ted B.; Palkovits, Miklós; Hasan, Mazahir T.; Grinevich, Valery & Dobolyi, Arpád
  
• Altered PVN‐to‐CA2 hippocampal oxytocin pathway and reduced number of oxytocin‐receptor expressing astrocytes in heart failure rats. Journal of Neuroendocrinology, 34(7).
  Althammer, Ferdinand; Roy, Ranjan K.; Lefevre, Arthur; Najjar, Rami S.; Schoenig, Kai; Bartsch, Dusan; Eliava, Marina; Feresin, Rafaela G.; Hammock, Elizabeth A. D.; Murphy, Anne Z.; Charlet, Alexandre; Grinevich, Valery & Stern, Javier E.
  
• Calcium imaging and BAPTA loading of amygdala astrocytes in mouse brain slices. STAR Protocols, 3(1), 101159.
  Baudon, Angel; Clauss-Creusot, Etienne; Darbon, Pascal; Patwell, Ryan; Grinevich, Valery & Charlet, Alexandre
  
• Compartmental Neuropeptide Release Measured Using a New Oxytocin Sensor. Cold Spring Harbor Laboratory.
  Qian, Tongrui; Wang, Huan; Wang, Peng; Geng, Lan; Mei, Long; Osakada, Takuya; Tang, Yan; Kania, Alan; Grinevich, Valery; Stoop, Ron; Lin, Dayu; Luo, Minmin & Li, Yulong
  
• Identification and three-dimensional reconstruction of oxytocin receptor expressing astrocytes in the rat and mouse brain. STAR Protocols, 3(1), 101160.
  Althammer, Ferdinand; Krause, Eric G.; de Kloet Anette, D.; Smith, Justin; Grinevich, Valery; Charlet, Alexandre & Stern, Javier E.
  
• Viral vectors for opto-electrode recording and photometry-based imaging of oxytocin neurons in anesthetized and socially interacting rats. STAR Protocols, 3(1), 101032.
  Tang, Yan; Benusiglio, Diego; Lefevre, Arthur; Küppers, Stephanie; Lapies, Olga; Kerspern, Damien; Charlet, Alexandre & Grinevich, Valery