Effect of relative social rank within a social hierarchy on neural activation in response to familiar or unfamiliar social signals

Abstract

Competent social functioning of group-living species relies on the ability of individuals to detect and utilize conspecific social cues to guide behavior. Previous studies have identified numerous brain regions involved in processing these external cues, collectively referred to as the Social Decision-Making Network. However, how the brain encodes social information with respect to an individual’s social status has not been thoroughly examined. In mice, cues about an individual’s identity, including social status, are conveyed through urinary proteins. In this study, we assessed the neural cFos immunoreactivity in dominant and subordinate male mice exposed to familiar and unfamiliar dominant and subordinate male urine. The posteroventral medial amygdala was the only brain region that responded exclusively to dominant compared to subordinate male urine. In all other brain regions, including the VMH, PMv, and vlPAG, activity is modulated by a combination of odor familiarity and the social status of both the urine donor and the subject receiving the cue. We show that dominant subjects exhibit robust differential activity across different types of cues compared to subordinate subjects, suggesting that individuals perceive social cues differently depending on social experience. These data inform further investigation of neurobiological mechanisms underlying social-status related brain differences and behavior.

Neural systems that facilitate the representation of social rank

“…In male mice ( Mus musculus ), specific receptors in the VNO have been identified as necessary for sex cue discrimination and expression of sexual and aggressive behaviour [ 26 , 27 ]. In both female and male mice, downstream targets of the VNO exhibit greater activation upon sniffing urine from dominant males compared to urine from subordinate males, as evidenced by number of cfos immunoreactive cells, a proxy of neuronal excitation [ 28 , 29 ]. This activity could represent the detection of higher levels of major urinary proteins (MUPs), some of which are crucial for territory marking [ 30 ].…”

“…Interestingly, in male mice, the MeA has more neurons with cfos immunoreactivity ( cfos -ir) after subjects are exposed to urine from an alpha (i.e. the most dominant individual in a hierarchy) compared to a subordinate conspecific, and this does not depend on the subject's own social rank or their familiarity with the cue source, although these factors may influence the biological relevance of the cue [ 29 ]. Activity in the MeA is also increased in both dominant and subordinate greater long-tailed hamsters ( Tscheskia triton ) following agonistic encounters and is not correlated to expression of aggression or defensive behaviour [ 42 ].…”

“…While the MeA plays a critical role in identifying social rank based on olfactory cues from mouse urine, it is not clear whether this process is further modified by social memory. Interestingly, several MeA hypothalamic projection targets are activated upon exposure to urine and are modulated by social rank and familiarity with the urine source [ 29 ]. For example, in the most subordinate mice from a hierarchy, differential cfos -ir within the ventromedial hypothalamic nucleus (VMH) is greater when they are exposed to alpha versus subordinate urine regardless of whether the urine is from a familiar mouse.…”

“…For example, in the most subordinate mice from a hierarchy, differential cfos -ir within the ventromedial hypothalamic nucleus (VMH) is greater when they are exposed to alpha versus subordinate urine regardless of whether the urine is from a familiar mouse. However, in the most dominant (alpha) mice from a hierarchy, cfos -ir in the VMH is only greater when they are exposed to unfamiliar alpha urine compared to either familiar or unfamiliar subordinate urine [ 29 ]. Thus, cfos -ir in the VMH upon exposure to urinary cues is modulated by familiarity with the cue, the social rank of the animal who provided the cue, and the animal processing the cue.…”

Human Primary Olfactory Amygdala Subregions Form Distinct Functional Networks, Suggesting Distinct Olfactory Functions

“…Most of our knowledge of the MeA comes from rodent work, which has shown that it is involved in a wide range of social behaviors (Lehman et al, 1980 ; Haller, 2018 ), and is a major constituent of the accessory olfactory system, receiving the bulk of monosynaptic projections from the accessory olfactory bulb (Mohedano-Moriano et al, 2007 ; Pro-Sistiaga et al, 2007 ). Within the accessory olfactory system, the MeA plays an important role in processing pheromonal signals and differentiating olfactory social cues including those that carry meaning about sex, age, and danger status (Bergan et al, 2014 ; Li et al, 2017 ; Yao et al, 2017 ; Lee et al, 2021 ). Social behaviors in rodents are strongly impacted by the main olfactory system (Keshavarzi et al, 2015 ; Pardo-Bellver et al, 2017 ), so it is likely that the MeA is involved in the processing of social cues that are encountered through the main olfactory system as well.…”