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. In many species, cues about an individual's identity, including social status, are conveyed through urinary proteins. 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 internal social status has not been thoroughly examined. Here we show that neuronal activity in male mice, as indicated by cFos immunoreactivity, is modulated by the social status and familiarity of the cue source and the subject's own social status. The posteroventral medial amygdala was the only brain region that responded exclusively to the social status of the cue source. Activity in other brain regions was modulated by social status. Specifically, within the brain of dominant subjects there was robust differential activity dependent on the status or familiarity of the cue source. Our results suggest that individuals perceive social cues differently depending on their social experience. These data inform further the investigation of neurobiological mechanisms underlying social-status related brain differences and how social status-associated differences influence physiology 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.…”

Social deficits in BTBR T+ Itpr3tf/J mice vary with ecological validity of the test

“…While much attention was given to examining the effects of solitude in mice and how stressful such rearing is, 73,74 it is important to recognize that living in a social group can also be a source of stress (for in-depth review please see Reference 18) with neuronal, endocrine and immune consequences, 16,31 which are not equal for each member of the group. 75,76 Dominant animals often experience stress related to constant challenging of their position by sub-dominants 72,77,78 which result with, among others, changes in gene expression in the hippocampus 79 not observed in subordinates. In the wild, mice display strong territoriality 80,81 which in laboratory emerges when living spaces are compartmentalized.…”