Gαi2+ vomeronasal neurons govern the initial outcome of an acute social competition

Abstract

frank Zufall 9 , pablo chamero 10 & José Luis trejo 11* pheromone detection by the vomeronasal organ (Vno) mediates important social behaviors across different species, including aggression and sexual behavior. However, the relationship between vomeronasal function and social hierarchy has not been analyzed reliably. We evaluated the role of pheromone detection by receptors expressed in the apical layer of the VNO such as vomeronasal type 1 receptors (V1R) in dominance behavior by using a conditional knockout mouse for G protein subunit Gαi2, which is essential for V1R signaling. We used the tube test as a model to analyze the within-acage hierarchy in male mice, but also as a paradigm of novel territorial competition in animals from different cages. In absence of prior social experience, Gαi2 deletion promotes winning a novel social competition with an unfamiliar control mouse but had no effect on an established hierarchy in cages with mixed genotypes, both Gαi2 −/− and controls. to further dissect social behavior of Gαi2 −/− mice, we performed a 3-chamber sociability assay and found that mutants had a slightly altered social investigation. Finally, gene expression analysis in the medial prefrontal cortex (mPFC) for a subset of genes previously linked to social status revealed no differences between group-housed Gαi2 −/− and controls. Our results reveal a direct influence of pheromone detection on territorial dominance, indicating that olfactory communication involving apical VNO receptors like V1R is important for the outcome of an initial social competition between two unfamiliar male mice, whereas final social status acquired within a cage remains unaffected. These results support the idea that previous social context is relevant for the development of social hierarchy of a group. Overall, our data identify two context-dependent forms of dominance, acute and chronic, and that pheromone signaling through V1R receptors is involved in the first stages of a social competition but in the long term is not predictive for high social ranks on a hierarchy. Social dominance comprises a set of behaviors related to the control of resources between animals of the same species, including access to territory, reproduction, and food 1. Such imposition can be either chronic or acute when animals face either repetitive or sporadic encounters. In group-living animals, repetitive encounters of animals living in the same group can lead to social dominance, i.e. social hierarchy, conditioned by the group's social history 2. In non-group living animals, territorial control can occur as a result of acute dyadic interactions 3 between animals with no record of previous contact. Whether these two different types of dominance are regulated by the same neural mechanisms is currently unclear.

Novel Competition test for food rewards reveals stable dominance status in adult male rats

“…The differences between the establishment of a hierarchy and its maintenance are starting to be explored, and the field would vastly benefit from new behavioral tools to address this fascinating question. Recent reports indicate that indeed these mechanisms are different in mice (Pallé et al , 2019, 2020) and our new behavioral task opens the possibility for the study of such differences in rats.…”

“…However, the establishment of social hierarchy might not rely on the same mechanisms as the expression of dominance when a hierarchy is already established. Recent reports in mice indicate that this is indeed the case (Pallé et al , 2019, 2020).…”

“…When taking into account the body weight of the animals, this relationship was significant, as shown by the regression of the number of pellets eaten in the modified Food Competition test and the how an animal would win in the first encounter in the Tube Test when regressing out body weight. Body weight has been largely assumed to be a good indicator of social hierarchy in rats (Macdonald, Berdoy and Smith, 1995), although this has not been replicated for mice (Wang, Kessels and Hu, 2014; Pallé et al , 2020). This view was inspired by classic works (Hoyenga and Rowe, 1969) and the seminal contributions in the field upon the development of the visible burrow system (Blanchard and Blanchard, 1989; Blanchard et al , 1995).…”

“…The most established view is that social hierarchy is built upon aggressive interactions (see Drews 1993 for a conceptual review), and serve as a mechanism of resources management and minimization of energy expenditure by groups of animals; once a hierarchy is established, priority access to resources is organized allowing the reduction of aggressive levels between the interacting animals (Vessey, 1981). Following this view, most of the behavioral paradigms available for measuring social hierarchy in laboratory animals are based in the nature of agonistic interactions while defending access to resources, whether a sexual partner,food or water when they are scarce, or the defense of a territory (Cordero and Sandi, 2007; Timmer and Sandi, 2010; Wang et al , 2011; Wang, Kessels and Hu, 2014; Hollis et al , 2015; Jupp et al , 2016; Zhou et al , 2017; Zhou, Sandi and Hu, 2018; Pallé et al , 2019, 2020).…”

Mechanisms underlying pre- and postnatal development of the vomeronasal organ

“…During the late embryonic and adult stages, the mouse VNO is mostly composed of two main classes of vomeronasal sensory neurons (VSNs) that each selectively expresses G protein coupled receptors (GPCRs) encoded by one of the two vomeronasal receptor (VR) gene families: V1R and V2R [22][23][24][25][26][27]. Hundreds of VSN subpopulations expressing V1Rs or V2Rs bind different ligands, trigger distinct innate behaviors, localize in different regions in the VNO and project to different areas in the accessory olfactory bulb (AOB) [4,[28][29][30][31][32]. V1R positive neurons lie mostly in the apical zone of the vomeronasal epithelium and express the G-protein subunit Gαi2 and neuropilin-2 (Nrp-2) and project to the anterior portion of the AOB [33,34].…”