Temporal microstructure of dyadic social behavior during relationship formation in mice

Autoři: Won Lee aff001;  Jiayi Fu aff002;  Neal Bouwman aff001;  Pam Farago aff001;  James P. Curley aff001
Působiště autorů: Department of Psychology, Columbia University, New York, New York, United States of America aff001;  Department of Statistics Graduate Program, Washington University in Saint Louis, Saint Louis, Missouri, United States of America aff002;  Department of Statistics Master’s Program, Columbia University, New York, New York, United States of America aff003;  Center for Integrative Animal Behavior, Columbia University, New York, New York, United States of America aff004;  Department of Psychology, University of Texas, Austin, Texas, United States of America aff005
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0220596


Socially competent animals must learn to modify their behavior in response to their social partner in a contextually appropriate manner. Dominant-subordinate relationships are a particularly salient social context for mice. Here we observe and analyze the microstructure of social and non-social behaviors as 21 pairs of outbred CD-1 male mice (Mus Musculus) establish dominant-subordinate relationships during daily 20-minute interactions for five consecutive days in a neutral environment. Firstly, using a Kleinberg burst detection algorithm, we demonstrate aggressive and subordinate interactions occur in bursting patterns followed by quiescent periods rather than being uniformly distributed across social interactions. Secondly, we identify three phases of dominant-subordinate relationship development (pre-, middle-, and post-resolution) by utilizing two statistical methods to identify stability in aggressive and subordinate behavior across these bursts. Thirdly, using First Order Markov Chains we find that dominant and subordinate mice show distinct behavioral transitions, especially between tail rattling and other aggressive/subordinate behaviors. Further, dominant animals engaged in more digging and allogrooming behavior and were more likely to transition from sniffing their partner’s body to head, whereas subordinates were more likely to transition from head sniffing to side-by-side contact. Lastly, we utilized a novel method (Forward Spike Time Tiling Coefficient) to assess how individuals respond to the behaviors of their partner. We found that subordinates decrease their tail rattling and aggressive behavior in response to aggressive but not subordinate behavior exhibited by dominants and that tail rattling in particular may function to deescalate aggressive behavior in pairs. Our findings demonstrate that CD-1 male mice rapidly establish dominance relationships and modify their social and non-social behaviors according to their current social status. The methods that we detail also provide useful tools for other researchers wishing to evaluate the temporal dynamics of rodent social behavior.

Klíčová slova:

Aggression – Animal behavior – Animal sociality – Biological locomotion – Interpersonal relationships – Mice – Microstructure – Social status


1. Hollis F, Kooij MA van der, Zanoletti O, Lozano L, Cantó C, Sandi C. Mitochondrial function in the brain links anxiety with social subordination. Proc Natl Acad Sci. 2015;112: 15486–15491. doi: 10.1073/pnas.1512653112 26621716

2. Drickamer LC. Urine marking and social dominance in male house mice (Mus musculus domesticus). Behav Processes. 2001;53: 113–120. doi: 10.1016/s0376-6357(00)00152-2 11254998

3. Cowan D, Gosling LM, Hudson J, Collins SA. Does behaviour after weaning affect the dominance status of adult male mice (Mus domesticus)? Behaviour. 1997;134: 989–1002.

4. Bartolomucci A. Social stress, immune functions and disease in rodents. Front Neuroendocrinol. 2007;28: 28–49. doi: 10.1016/j.yfrne.2007.02.001 17379284

5. Zhou T, Sandi C, Hu H. Advances in understanding neural mechanisms of social dominance. Curr Opin Neurobiol. 2018;49: 99–107. doi: 10.1016/j.conb.2018.01.006 29428628

6. Taborsky B, Oliveira RF. Social competence: an evolutionary approach. Trends Ecol Evol. 2012;27: 679–688. doi: 10.1016/j.tree.2012.09.003 23040461

7. Chase ID, Tovey C, Spangler-Martin D, Manfredonia M. Individual differences versus social dynamics in the formation of animal dominance hierarchies. Proc Natl Acad Sci. 2002;99: 5744–5749. doi: 10.1073/pnas.082104199 11960030

8. Maestripieri D, De Simone R, Aloe L, Alleva E. Social status and nerve growth factor serum levels after agonistic encounters in mice. Physiol Behav. 1990;47: 161–164. doi: 10.1016/0031-9384(90)90056-a 2326332

9. Drews C. The concept and definition of dominance in animal behaviour. Behaviour. 1993;125: 283–313.

10. Espejo EF. Structure of the mouse behaviour on the elevated plus-maze test of anxiety. Behav Brain Res. 1997;86: 105–112. doi: 10.1016/s0166-4328(96)02245-0 9105588

11. Pisula W. Sequential Analysis of Rat Behavior in th Open Field. Int J Comp Psychol. 1994;7. Available: https://escholarship.org/uc/item/6vz360gc

12. Pisula W, Osiński JT. A Comparative Study of the Behavioral Patterns of RLA/Verh and RHA/Verh Rats in the Exploration Box. Behav Genet. 2000;30: 375–384. doi: 10.1023/a:1002748521117 11235983

13. Tejada J, Bosco GG, Morato S, Roque AC. Characterization of the rat exploratory behavior in the elevated plus-maze with Markov chains. J Neurosci Methods. 2010;193: 288–295. doi: 10.1016/j.jneumeth.2010.09.008 20869398

14. Lino-de-Oliveira C, Lima TCMD, Carobrez A de P. Structure of the rat behaviour in the forced swimming test. Behav Brain Res. 2005;158: 243–250. doi: 10.1016/j.bbr.2004.09.004 15698890

15. Brain PF, Brain S, Benton D. Ethological analyses of the effects of naloxone and the opiate antagonist ICI 154, 129 on social interactions in male house mice. Behav Processes. 1985;10: 341–354. doi: 10.1016/0376-6357(85)90035-X 24897570

16. Brain PF, Smoothy R, Benton D. An ethological analysis of the effects of tifluadom on social encounters in male albino mice. Pharmacol Biochem Behav. 1985;23: 979–985. doi: 10.1016/0091-3057(85)90104-2 3001788

17. Miczek KA, Haney M, Tidey J, Vatne T, Weerts E, DeBold JF. Temporal and sequential patterns of agonistic behavior: effects of alcohol, anxiolytics and psychomotor stimulants. Psychopharmacology (Berl). 1989;97: 149–151.

18. Natarajan D, de Vries H, de Boer SF, Koolhaas JM. Violent phenotype in SAL mice is inflexible and fixed in adulthood. Aggress Behav. 2009;35: 430–436. doi: 10.1002/ab.20312 19533684

19. Natarajan D, de Vries H, Saaltink D-J, de Boer SF, Koolhaas JM. Delineation of violence from functional aggression in mice: an ethological approach. Behav Genet. 2009;39: 73–90. doi: 10.1007/s10519-008-9230-3 18972199

20. Van Den Berg CL, Van Ree JM, Spruijt BM. Sequential Analysis of Juvenile Isolation-Induced Decreased Social Behavior in the Adult Rat. Physiol Behav. 1999;67: 483–488. doi: 10.1016/s0031-9384(99)00062-1 10549885

21. Vanderschuren LJ, Spruijt BM, Hol T, Niesink RJ, Van Ree JM. Sequential analysis of social play behavior in juvenile rats: effects of morphine. Behav Brain Res. 1995;72: 89–95. doi: 10.1016/0166-4328(96)00060-5 8788861

22. Miczek KA, Weerts EM, Tornatzky W, DeBold JF, Vatne TM. Alcohol and “bursts” of aggressive behavior: ethological analysis of individual differences in rats. Psychopharmacology (Berl). 1992;107: 551–563.

23. Caramaschi D, de Boer SF, de Vries H, Koolhaas JM. Development of violence in mice through repeated victory along with changes in prefrontal cortex neurochemistry. Behav Brain Res. 2008;189: 263–272. doi: 10.1016/j.bbr.2008.01.003 18281105

24. Spruijt BM. Progressive decline in social attention in aging rats: an information-statistical method. Neurobiol Aging. 1992;13: 145–151. doi: 10.1016/0197-4580(92)90022-p 1542375

25. Yamada-Haga Y. Characteristics of social interaction between unfamiliar male rats (Rattus norvegicus): comparison of juvenile and adult stages. J Ethol. 2014;20: 55–62. doi: 10.1007/s10164-002-0054-y

26. Chorney JM, Garcia AM, Berlin KS, Bakeman R, Kain ZN. Time-Window Sequential Analysis: An Introduction for Pediatric Psychologists. J Pediatr Psychol. 2010;35: 1061–1070. doi: 10.1093/jpepsy/jsq022 20392791

27. Koyama S. Isolation effect in mice (Mus musculus): (i) Does it really induce aggression? J Ethol. 1993;11: 117–130. doi: 10.1007/BF02350045

28. Yoder PJ, Tapp J. Empirical Guidance for Time-Window Sequential Analysis of Single Cases. J Behav Educ. 2004;13: 227–246. doi: 10.1023/B:JOBE.0000044733.03220.a9

29. Branchi I, Curley JP, D’Andrea I, Cirulli F, Champagne FA, Alleva E. Early interactions with mother and peers independently build adult social skills and shape BDNF and oxytocin receptor brain levels. Psychoneuroendocrinology. 2013;38: 522–532. doi: 10.1016/j.psyneuen.2012.07.010 22910688

30. Cutts CS, Eglen SJ. Detecting pairwise correlations in spike trains: an objective comparison of methods and application to the study of retinal waves. J Neurosci Off J Soc Neurosci. 2014;34: 14288–14303. doi: 10.1523/JNEUROSCI.2767-14.2014 25339742

31. Bürkner P-C. brms: Bayesian Regression Models using Stan. 2018. Available: https://CRAN.R-project.org/package=brms

32. Gelman A, Rubin DB. Inference from Iterative Simulation Using Multiple Sequences. Stat Sci. 1992;7: 457–472. doi: 10.1214/ss/1177011136

33. Carpenter B, Gelman A, Hoffman MD, Lee D, Goodrich B, Betancourt M, et al. Stan: A Probabilistic Programming Language. J Stat Softw Vol 1 Issue 1 2017. 2017. Available: https://www.jstatsoft.org/v076/i01

34. Bursty Kleinberg J. and Hierarchical Structure in Streams. Data Min Knowl Discov. 2003;7: 373–397. doi: 10.1023/A:1024940629314

35. Binder J. bursts: Markov model for bursty behavior in streams. 2014. Available: https://cran.r-project.org/web/packages/bursts/index.html

36. McNemar Q. Psychological Statistics. New York: John Wiley & Sons; 1962.

37. Gottman JM, Roy AK. Sequential Analysis. A guide for behavioral researchers. Cambridge: Cambridge University Press; 1990.

38. Blocker AW. ipfp: Fast Implementation of the Iterative Proportional Fitting Procedure in C. 2016. Available: https://cran.r-project.org/web/packages/ipfp/index.html

39. Bakeman R, Robinson BF, Quera V. Testing sequential association: Estimating exact p values using sampled permutations. Psychol Methods. 1996;1: 4–15. doi: 10.1037/1082-989X.1.1.4

40. López P, Martín J. Fighting rules and rival recognition reduce costs of aggression in male lizards, Podarcis hispanica. Behav Ecol Sociobiol. 2001;49: 111–116. doi: 10.1007/s002650000288

41. Morris MR, Gass L, Ryan MJ. Assessment and individual recognition of opponents in the pygmy swordtails Xiphophorus nigrensis and X. multilineatus. Behav Ecol Sociobiol. 1995;37: 303–310. doi: 10.1007/BF00174134

42. Tanner CJ, Adler FR. To fight or not to fight: context-dependent interspecific aggression in competing ants. Anim Behav. 2009;77: 297–305. doi: 10.1016/j.anbehav.2008.10.016

43. Guhl AM. Social inertia and social stability in chickens. Anim Behav. 1968;16: 219–232. doi: 10.1016/0003-3472(68)90003-1 5691847

44. Alleva E. 7—Assessment of Aggressive Behavior in Rodents* *To Giuseppe Montalenti, my master of natural sciences, rigor, and, hopefully, style. In: Conn PM, editor. Methods in Neurosciences. Academic Press; 1993. pp. 111–137. doi: 10.1016/B978-0-12-185277-1.50012–5

45. Archer J. The Behavioural Biology of Aggression. CUP Archive; 1988.

46. Marden JH, Waage JK. Escalated damselfly territorial contests are energetic wars of attrition. Anim Behav. 1990;39: 954–959. doi: 10.1016/S0003-3472(05)80960-1

47. Kooij MA van der, Fantin M, Kraev I, Korshunova I, Grosse J, Zanoletti O, et al. Impaired Hippocampal Neuroligin-2 Function by Chronic Stress or Synthetic Peptide Treatment is Linked to Social Deficits and Increased Aggression. Neuropsychopharmacology. 2014;39: 1148–1158. doi: 10.1038/npp.2013.315 24213355

48. Larrieu T, Cherix A, Duque A, Rodrigues J, Lei H, Gruetter R, et al. Hierarchical Status Predicts Behavioral Vulnerability and Nucleus Accumbens Metabolic Profile Following Chronic Social Defeat Stress. Curr Biol. 2017;27: 2202–2210.e4. doi: 10.1016/j.cub.2017.06.027 28712571

49. Krackow S. Motivational and Heritable Determinants of Dispersal Latency in Wild Male House Mice (Mus musculus musculus). Ethology. 2003;109: 671–689. doi: 10.1046/j.1439-0310.2003.00913.x

50. Sundström LF, Petersson E, Höjesjö J, Johnsson JI, Järvi T. Hatchery selection promotes boldness in newly hatched brown trout (Salmo trutta): implications for dominance. Behav Ecol. 2004;15: 192–198. doi: 10.1093/beheco/arg089

51. Blanchard RJ, Flores T, Magee L, Weiss S, Blanchard DC. Pregrouping aggression and defense scores influences alcohol consumption for dominant and subordinate rats in visible burrow systems. Aggress Behav. 1992;18: 459–467. doi: 10.1002/1098-2337(1992)18:6<459::AID-AB2480180608>3.0.CO;2-P

52. Beaugrand JP, Payette D, Goulet C. Conflict Outcome in Male Green Swordtail Fish Dyads (Xiphophorus Helleri): Interaction of Body Size, Prior Dominance/Subordination Experience, and Prior Residency. Behaviour. 1996;133: 303–319. doi: 10.1163/156853996X00161

53. Fuxjager MJ, Forbes-Lorman RM, Coss DJ, Auger CJ, Auger AP, Marler CA. Winning territorial disputes selectively enhances androgen sensitivity in neural pathways related to motivation and social aggression. Proc Natl Acad Sci. 2010;107: 12393–12398. doi: 10.1073/pnas.1001394107 20616093

54. Curley JP. Temporal pairwise-correlation analysis provides empirical support for attention hierarchies in mice. Biol Lett. 2016;12: 20160192. doi: 10.1098/rsbl.2016.0192 27194290

55. Lindquist WB, Chase ID. Data-based analysis of winner-loser models of hierarchy formation in animals. Bull Math Biol. 2009;71: 556–584. doi: 10.1007/s11538-008-9371-9 19205807

56. Bakeman R, Quera V. Sequential Analysis and Observational Methods for the Behavioral Sciences. 1st ed. Cambridge: Cambridge University Press; 2011.

57. Martinez M, Calvo‐Torrent A, Pico‐Alfonso MA. Social defeat and subordination as models of social stress in laboratory rodents: A review. Aggress Behav. 1998;24: 241–256. doi: 10.1002/(SICI)1098-2337(1998)24:4<241::AID-AB1>3.0.CO;2-M

58. Russo SJ, Murrough JW, Han M-H, Charney DS, Nestler EJ. Neurobiology of resilience. Nat Neurosci. 2012;15: 1475–1484. doi: 10.1038/nn.3234 23064380

59. Choi GB, Dong H, Murphy AJ, Valenzuela DM, Yancopoulos GD, Swanson LW, et al. Lhx6 Delineates a Pathway Mediating Innate Reproductive Behaviors from the Amygdala to the Hypothalamus. Neuron. 2005;46: 647–660. doi: 10.1016/j.neuron.2005.04.011 15944132

60. Falkner AL, Grosenick L, Davidson TJ, Deisseroth K, Lin D. Hypothalamic control of male aggression-seeking behavior. Nat Neurosci. 2016;19: 596–604. doi: 10.1038/nn.4264 26950005

61. Hong W, Kim D-W, Anderson DJ. Antagonistic Control of Social versus Repetitive Self-Grooming Behaviors by Separable Amygdala Neuronal Subsets. Cell. 2014;158: 1348–1361. doi: 10.1016/j.cell.2014.07.049 25215491

62. Miczek KA, Maxson SC, Fish EW, Faccidomo S. Aggressive behavioral phenotypes in mice. Behav Brain Res. 2001;125: 167–181. doi: 10.1016/s0166-4328(01)00298-4 11682108

63. Krsiak M. Tail rattling in aggressive mice as a measure of tranquillizing activity of drugs. Act Nerv Super (Praha). 1975.

64. Scott JP. “Emotional” behavior of fighting mice caused by conflict between weak stimulatory and weak inhibitory training. J Comp Physiol Psychol. 1947;40: 275. doi: 10.1037/h0057780 20260239

65. Clark LH, Schein MW. Activities associated with conflict behaviour in mice. Anim Behav. 1966;14: 44–49. doi: 10.1016/s0003-3472(66)80009-x 5950571

66. McFarlane HG, Kusek GK, Yang M, Phoenix JL, Bolivar VJ, Crawley JN. Autism-like behavioral phenotypes in BTBR T+tf/J mice. Genes Brain Behav. 2008;7: 152–163. doi: 10.1111/j.1601-183X.2007.00330.x 17559418

67. Mackintosh JH, Grant EC. A Comparison of the Social Postures of Some Common Laboratory Rodents. Behaviour. 1963;21: 246–259. doi: 10.1163/156853963X00185

68. Terranova ML, Laviola G, de Acetis L, Alleva E. A description of the ontogeny of mouse agonistic behavior. J Comp Psychol. 1998;112: 3–12. doi: 10.1037/0735-7036.112.1.3 9528111

69. Curley JP. Is there a genomically imprinted social brain? Bioessays. 2011;33: 662–668. doi: 10.1002/bies.201100060 21805481

70. Kalueff AV, Keisala T, Minasyan A, Kuuslahti M, Tuohimaa P. Temporal stability of novelty exploration in mice exposed to different open field tests. Behav Processes. 2006;72: 104–112. doi: 10.1016/j.beproc.2005.12.011 16442749

71. Long SY. Hair-nibbling and whisker-trimming as indicators of social hierarchy in mice. Anim Behav. 1972;20: 10–12. doi: 10.1016/s0003-3472(72)80167-2 4677163

72. Sarna JR, Dyck RH, Whishaw IQ. The Dalila effect: C57BL6 mice barber whiskers by plucking. Behav Brain Res. 2000;108: 39–45. doi: 10.1016/s0166-4328(99)00137-0 10680755

73. Bresnahan JF, Kitchell BB, Wildman MF. Facial hair barbering in rats. Lab Anim Sci. 1983;33: 290–291. 6876735

74. Rieder CA, Reynierse JH. Effects of maintenance condition on aggression and marking behavior of the Mongolian gerbil (Meriones unguiculatus). J Comp Physiol Psychol. 1971;75: 471–475. doi: 10.1037/h0030952

75. Kudryavtseva NN. Agonistic behavior: A model, experimental studies, and perspectives. Neurosci Behav Physiol. 2000;30: 293–305. doi: 10.1007/bf02471782 10970023

76. Kudryavtseva NN, Smagin DA, Kovalenko IL, Vishnivetskaya GB. Repeated positive fighting experience in male inbred mice. Nat Protoc. 2014;9: 2705–2717. doi: 10.1038/nprot.2014.156 25340443

77. Koyama S. Isolation effect in mice (Mus musculus): (ii) Variance in aggression. J Ethol. 1993;11: 131–140. doi: 10.1007/BF02350046

78. Vekovischeva OY, Semenova SG, Verbitskaya EV, Zvartau EE. Effects of morphine and cocaine in mice with stable high aggressive and nonaggressive behavioral strategy. Pharmacol Biochem Behav. 2004;77: 235–243. doi: 10.1016/j.pbb.2003.10.021 14751450

79. Wesson DW. Sniffing Behavior Communicates Social Hierarchy. Curr Biol. 2013;23: 575–580. doi: 10.1016/j.cub.2013.02.012 23477727

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