Using the tube test to measure social hierarchy in mice

Fan, Zhengxiao; Hong, Zhu; Zhou, Tingting; Wang, Sheng; Wu, Yan; Hu, Hailan

doi:10.1038/s41596-018-0116-4

Cited by 108 publications

(97 citation statements)

References 60 publications

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“…defensive or aggressive) is elicited by introducing an intruder into the home cage of the resident (Miczek et al, 2001). In tube test assays, two mice interact in a tube large enough to allow head-to-head interactions— but not aggressive fighting—until one mouse, the loser, exits the tube (Fan et al, 2019). Iterative tube test tournaments provide clear binary outcomes for each trial and have been shown to provide a readout of hierarchical relationships supported by the outcomes of other dominance-subordinate assays tested (Wang et al, 2011).…”

Section: Resultsmentioning

confidence: 99%

Molecular and Circuit Architecture of Social Hierarchy

Nelson

Kapoor

Vaughn

et al. 2019

Preprint

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1 4 nearly 20 areas sent mono-synaptic inputs to MDT Glut neurons, including hypothalamic areas associated with arousal, feeding, and pain (e.g., lateral hypothalamus (LH), preoptic area (POA)), basal forebrain areas associated with reward learning and voluntary movement (e.g., NDB, ventral pallidum (VP), substantia innominata (SI)), deep-layer cortical areas associated with executive function (ACC, OFC, PL), areas associated with olfaction (piriform cortex, olfactory tubercle, OFC), and intra-thalamic information processing areas (reticular thalamus and zona incerta) ( Fig. 3B-C).Projections from MDT Glut neurons were visualized using two combined AAVs driving expression of reporter fluorophores in axons (tdTomato) and presynaptic terminals (Synaptophysin-GFP fusion protein) ( Fig. 3D). As previously described, layer II/III in cortical areas associated with executive, perceptual and memory functions (e.g., ACC, OFC, PL) received the majority of MDT Glut projections (Delevich et al., 2015; Krettek and Price, 1977). The ACC, from its most rostral (> bregma +2.0) to caudal (< bregma -2.0) coordinates, received the greatest fraction of inputs ( Fig. 3E-F). Additional targets included cortical (retrosplenial and infralimbic cortex) and basal ganglia areas (i.e., globus pallidus, dorsomedial caudate putamen, and nucleus accumbens). The MDT Glut circuit is therefore poised to integrate aspects of learned interactions, emotional valance, innate behavioral responses, and olfactory communication, all functions that are highly relevant to hierarchy formation. Activity of MDT-cAAC projections during social competitionThe cACC, a major target of MDT Glut projections, showed decreased activity in rank-1 males after tube tests ( Fig. 2A). Because rank-1 males showed increased activity in MDT, we hypothesized that MDT may inhibit the cACC. Indeed, reports using viral tracing (Delevich et al., 2015; Lu et al., 2017), optogenetic assisted circuit mapping (Delevich et al., 2015; Ferguson and Gao, 2018; Miller et al., 2017), and neurophysiological studies of decision making (Schmitt et al., 2017) suggest that MDT projections can drive feedforward inhibition of the PFC through

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Section: Resultsmentioning

confidence: 99%

Molecular and Circuit Architecture of Social Hierarchy

Nelson

Kapoor

Vaughn

et al. 2019

Preprint

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“…If the mouse remained stationary for longer than 5s, or began retreating, a gentle push from behind was used to direct movement towards the middle door. The use of food deprivation and food reward previously showed no effect on animals' motivation to complete the task [18] and was therefore not used in this study.…”

Section: Social Confrontation Tube Test (Tt)mentioning

confidence: 99%

“…Both in the wild and in the lab, dominance hierarchies are readily observable due to the distinct patterns of behavioural characteristics in the different social ranks (reviewed in [17]). One of standard tests of dominance in mice is the competitive exclusion task or the "tube test" [18], first developed to study dominance differences between inbred strains [19]. This dyadic test offers clear and binary scoring of dominance, based on the use of space resources, that would otherwise be difficult to assess directly in the home cage.…”

Section: Introductionmentioning

confidence: 99%

What it takes to be at the top: The interrelationship between chronic social stress and social dominance

Šabanović

Mlambo

et al. 2020

Preprint

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AbstractDominance hierarchies of social animal groups are influenced by complex factors such as stress. Stress experienced by an animal prior to social interactions with a conspecific may be a determinant of their future social dynamics. Additionally, long-term occupancy of a specific hierarchical rank can have psychophysiological effects, leading to vulnerability to future stress.The current study aimed to delineate differential effects of stress acting before or after hierarchy formation. Using the chronic social defeat stress (CSDS) paradigm we performed behavioural investigations to determine whether exposure to CSDS before hierarchy formation predicted the new dominance status. Moreover, in another study we investigated whether social rank predicted stress vulnerability.We found that CSDS did not impede the establishment of dominance in new hierarchies as both stress-susceptible (socially avoidant) and –resilient (social) mice were able to attain dominant ranks. In contrast, within newly established hierarchies of stress-naïve mice, the subordinate, but not dominant, mice exhibit significantly greater avoidance of novel social targets. However, following exposure to CSDS, both lowest- and highest-ranked mice exhibit strong susceptibility to stress as measured by decreased interactions with a novel social target.These results suggest that the response to chronic social stress did not determine social rank in new cohorts, but low-status mice in newly established groups exhibited lower sociability to novel social targets. Interestingly, exposure of a hierarchical social group to chronic social stress led to stress-susceptibility in both high- and low-status mice as measured by social interaction.HighlightsStress susceptibility to chronic social defeat did not impede the establishment of dominance in new hierarchies.Subordinate mice exhibit reduced social preference after hierarchy formation.Following chronic social defeat stress, both subordinate and dominant mice exhibit susceptible-like reduction in social interaction, but dominant mice exhibit the greater decrease in social preference as compared to baseline.

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“…Social dominance. To assess social dominance, we implemented the tube test assay [39]. A clear acrylic tube with inner diameter of 25 mm and length of 12 cm was used.…”

Section: Behaviormentioning

confidence: 99%

“…However, not all behaviors were affected by the prefrontal lentiviral manipulation. For social dominance, we adapted the tube test in which two animals faced each other inside a narrow tube and losing was defined by retreat [39]. Against SST-Cre controls, the SST-Cre/R1117X +/+ animals won frequently, and the dominance remained after lentiviral manipulation (Fig.…”

Section: Effects Of Restoring Dendritic Inhibition On Social- Anxietmentioning

confidence: 99%

Inhibitory regulation of calcium transients in prefrontal dendritic spines is compromised by a nonsenseShank3mutation

Ali

Shao

Gerhard

et al. 2020

Preprint

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The SHANK3 gene encodes a postsynaptic scaffold protein in excitatory synapses, and its disruption is implicated in neurodevelopmental disorders such as Phelan-McDermid syndrome, autism spectrum disorder, and schizophrenia. Most studies of SHANK3 in the neocortex and hippocampus have focused on disturbances in pyramidal neurons. However, GABAergic interneurons likewise receive excitatory inputs and presumably would also be a target of constitutive SHANK3 perturbations. In this study, we characterize the prefrontal cortical microcircuit in awake mice using subcellular-resolution two-photon microscopy. We focused on a nonsense R1117X mutation, which leads to truncated SHANK3 and has been linked previously to cortical dysfunction. We find that R1117X mutants have abnormally elevated calcium transients in apical dendritic spines. The synaptic calcium dysregulation is due to a loss of dendritic inhibition via decreased NMDAR currents and reduced firing of dendrite-targeting somatostatin-expressing (SST) GABAergic interneurons. Notably, upregulation of the NMDAR subunit GluN2B in SST interneurons corrects the excessive synaptic calcium signals and ameliorates learning deficits in R1117X mutants. These findings reveal dendrite-targeting interneurons, and more broadly the inhibitory control of dendritic spines, as a key microcircuit mechanism compromised by the SHANK3 dysfunction.

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Using the tube test to measure social hierarchy in mice

Cited by 108 publications

References 60 publications

Molecular and Circuit Architecture of Social Hierarchy

Molecular and Circuit Architecture of Social Hierarchy

What it takes to be at the top: The interrelationship between chronic social stress and social dominance

Inhibitory regulation of calcium transients in prefrontal dendritic spines is compromised by a nonsenseShank3mutation

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