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A Social Network Approach Reveals Associations between Mouse Social Dominance and Brain Gene Expression.

ABSTRACT: Modelling complex social behavior in the laboratory is challenging and requires analyses of dyadic interactions occurring over time in a physically and socially complex environment. In the current study, we approached the analyses of complex social interactions in group-housed male CD1 mice living in a large vivarium. Intensive observations of social interactions during a 3-week period indicated that male mice form a highly linear and steep dominance hierarchy that is maintained by fighting and chasing behaviors. Individual animals were classified as dominant, sub-dominant or subordinate according to their David's Scores and I& SI ranking. Using a novel dynamic temporal Glicko rating method, we ascertained that the dominance hierarchy was stable across time. Using social network analyses, we characterized the behavior of individuals within 66 unique relationships in the social group. We identified two individual network metrics, Kleinberg's Hub Centrality and Bonacich's Power Centrality, as accurate predictors of individual dominance and power. Comparing across behaviors, we establish that agonistic, grooming and sniffing social networks possess their own distinctive characteristics in terms of density, average path length, reciprocity out-degree centralization and out-closeness centralization. Though grooming ties between individuals were largely independent of other social networks, sniffing relationships were highly predictive of the directionality of agonistic relationships. Individual variation in dominance status was associated with brain gene expression, with more dominant individuals having higher levels of corticotropin releasing factor mRNA in the medial and central nuclei of the amygdala and the medial preoptic area of the hypothalamus, as well as higher levels of hippocampal glucocorticoid receptor and brain-derived neurotrophic factor mRNA. This study demonstrates the potential and significance of combining complex social housing and intensive behavioral characterization of group-living animals with the utilization of novel statistical methods to further our understanding of the neurobiological basis of social behavior at the individual, relationship and group levels.

SUBMITTER: So N

PROVIDER: S-EPMC4520683 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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A Social Network Approach Reveals Associations between Mouse Social Dominance and Brain Gene Expression.

So Nina N Franks Becca B Lim Sean S Curley James P JP

PloS one 20150730 7

Modelling complex social behavior in the laboratory is challenging and requires analyses of dyadic interactions occurring over time in a physically and socially complex environment. In the current study, we approached the analyses of complex social interactions in group-housed male CD1 mice living in a large vivarium. Intensive observations of social interactions during a 3-week period indicated that male mice form a highly linear and steep dominance hierarchy that is maintained by fighting and ...[more]

PMID: 26226265

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Project description:ImportanceCognitive impairment occurs across the psychosis spectrum and is associated with functional outcome. However, it is unknown whether these shared manifestations of cognitive dysfunction across diagnostic categories also reflect shared neurobiological mechanisms or whether the source of impairment differs.ObjectiveTo examine whether the general cognitive deficit observed across psychotic disorders is similarly associated with functional integrity of 2 brain networks widely implicated in supporting many cognitive domains.Design, setting, and participantsA total of 201 healthy control participants and 375 patients with psychotic disorders from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium were studied from September 29, 2007, to May 31, 2011. The B-SNIP recruited healthy controls and stable outpatients from 6 sites: Baltimore, Maryland; Boston, Massachusetts; Chicago, Illinois; Dallas, Texas; Detroit, Michigan; and Hartford, Connecticut. All participants underwent cognitive testing and resting-state functional magnetic resonance imaging. Data analysis was performed from April 28, 2015, to February 21, 2017.Main outcomes and measuresThe Brief Assessment of Cognition in Schizophrenia was used to measure cognitive ability. A principal axis factor analysis on the Brief Assessment of Cognition in Schizophrenia battery yielded a single factor (54% variance explained) that served as the measure of general cognitive ability. Functional network integrity measures included global and local efficiency of the whole brain, cingulo-opercular network (CON), frontoparietal network, and auditory network and exploratory analyses of all networks from the Power atlas. Group differences in network measures, associations between cognition and network measures, and mediation models were tested.ResultsThe final sample for the current study included 201 healthy controls, 143 patients with schizophrenia, 103 patients with schizoaffective disorder, and 129 patients with psychotic bipolar disorder (mean [SD] age, 35.1 [12.0] years; 281 male [48.8%] and 295 female [51.2%]; 181 white [31.4%], 348 black [60.4%], and 47 other [8.2%]). Patients with schizophrenia (Cohen d = 0.36, P < .001) and psychotic bipolar disorder (Cohen d = 0.33, P = .002) had significantly reduced CON global efficiency compared with healthy controls. All patients with psychotic disorders had significantly reduced CON local efficiency, but the clinical groups did not differ from one another. The CON global efficiency was significantly associated with general cognitive ability across all groups (β = 0.099, P = .009) and significantly mediated the association between psychotic disorder status and general cognition (β = -0.037; 95% CI, -0.076 to -0.014). Subcortical network global efficiency was also significantly reduced in psychotic disorders (F3,587 = 4.01, P = .008) and positively predicted cognitive ability (β = 0.094, P = .009).Conclusions and relevanceThese findings provide evidence that reduced CON and subcortical network efficiency play a role in the general cognitive deficit observed across the psychosis spectrum. They provide new support for the dimensional hypothesis that a shared neurobiological mechanism underlies cognitive impairment in psychotic disorders.

Dataset Information

A Social Network Approach Reveals Associations between Mouse Social Dominance and Brain Gene Expression.

Publications

A Social Network Approach Reveals Associations between Mouse Social Dominance and Brain Gene Expression.

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