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Longitudinal Assessment of Deliberate Mouse Behavior in the Home Cage and Attached Environments: Relevance to Anxiety and Mood Disorders

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Mood and Anxiety Related Phenotypes in Mice

Part of the book series: Neuromethods ((NM,volume 63))

Abstract

Understanding behavioral regulation can further progress by developing new approaches that allow refinement of behavioral phenotypes. The current availability of several thousand different mutant mice and of human candidate genes for emotional (affective) disorders challenges behavioral neuroscientists to extend their views and methodologies to dissect complex behaviors into behavioral phenotypes and subsequently to define gene–behavioral phenotype relationships. Here, we put forward multiday automated behavioral and physiological observations in carefully designed environments to assess evolutionary conserved behavioral strategies in mice. This offers the opportunity to design experimental setups that allow the animals themselves to regulate their own behavior, using representations of continuous kinematic variables, studying the dynamics of behavior (change across time or change across activity); i.e., growth or decay processes of behavior and concomitant physiological adjustments such as heart rate. The measures characterizing these processes should have discriminative power (across strains or treatments) and be replicable (across laboratories). Furthermore, cross species genetic studies for these neurobehavioral and physiological traits may provide a novel way toward identifying neurobiological mechanisms underlying core features of complex psychiatric disorders.

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References

  1. Hall CS, . Emotional behavior in the rat I. Defecation and urination as measures of individual differences in emotionality. J Comp Psychol 1934; 18:385–403.

    Article  Google Scholar 

  2. Hall CS. Emotional behavior in the rat. III The relationship between emotionality and ambulatory activity. J Comp Psychol 1936; 22:345–352.

    Article  Google Scholar 

  3. Pellow S, Chopin P, File SE, Briley M. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 1985; 14(3):149–167.

    Article  PubMed  CAS  Google Scholar 

  4. Crawley JN, Goodwin FK. Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines. Pharmacol Biochem Behav 1980; 13:167–170.

    Article  PubMed  CAS  Google Scholar 

  5. Gerlai R. Phenomics: fiction or the future? Trends Neurosci 2002; 25(10):506–509.

    Article  PubMed  Google Scholar 

  6. Wahlsten D, Rustay NR, Metten P, Crabbe JC. In search of a better mouse test. Trends Neurosci 2003; 26(3):132–136.

    Article  PubMed  CAS  Google Scholar 

  7. Koolhaas JM, De Boer SF, Buwalda B. Stress and Adaptation: Toward Ecologically Relevant Animal Models. Current directions in psychological science 2006; 15(3):109–112.

    Article  Google Scholar 

  8. Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM. Dopaminergic role in stimulant-induced wakefulness. J Neurosci 2001; 21(5):1787–1794.

    PubMed  CAS  Google Scholar 

  9. Gainetdinov RR, Wetsel WC, Jones SR, Levin ED, Jaber M, Caron MG. Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity. Science 1999; 283(5400):397–401.

    Article  PubMed  CAS  Google Scholar 

  10. Dudley CA, Erbel-Sieler C, Estill SJ, Reick M, Franken P, Pitts S et al. Altered patterns of sleep and behavioral adaptability in NPAS2-deficient mice. Science 2003; 301(5631):379–383.

    Article  PubMed  CAS  Google Scholar 

  11. Drozdowicz CK, Bowman TA, Webb ML, Lang CM. Effect of in-house transport on murine plasma corticosterone concentration and blood lymphocyte populations. Am J Vet Res 1990; 51(11):1841–1846.

    PubMed  CAS  Google Scholar 

  12. Van Ree JM, De Wied D. Behavioral approach to the study of the rat brain. Discussions in Neurosciences 1988; 5(1):11–60.

    Google Scholar 

  13. Chesler EJ, Wilson SG, Lariviere WR, Rodriguez-Zas SL, Mogil JS. Influences of laboratory environment on behavior. Nat Neurosci 2002; 5(11):1101–1102.

    Article  PubMed  CAS  Google Scholar 

  14. Crabbe JC, Wahlsten D, Dudek BC. Genetics of mouse behavior: interactions with laboratory environment. Science 1999; 284(5420):1670–1672.

    Article  PubMed  CAS  Google Scholar 

  15. McIlwain KL, Merriweather MY, Yuva-Paylor LA, Paylor R. The use of behavioral test batteries: effects of training history. Physiol Behav 2001; 73(5):705–717.

    Article  PubMed  CAS  Google Scholar 

  16. Daan S, Pittendrigh CS. A functional analysis of circadian pacemakers in nocturnal rodents. II. The variability of the phase response curve. J Comp Physiol 1976; 106:253–266.

    Article  Google Scholar 

  17. Hastings MH, Duffield GE, Ebling FJ, Kidd A, Maywood ES, Schurov I. Non-photic signalling in the suprachiasmatic nucleus. Biol Cell 1997; 89(8):495–503.

    Article  PubMed  CAS  Google Scholar 

  18. Kafkafi N, Benjamini Y, Sakov A, Elmer GI, Golani I. Genotype-environment interactions in mouse behavior: a way out of the problem. Proc Natl Acad Sci USA 2005; 102(12):4619–4624.

    Article  PubMed  CAS  Google Scholar 

  19. Benjamini Y, Lipkind D, Horev G, Fonio E, Kafkafi N, Golani I. Ten ways to improve the quality of descriptions of whole-animal movement. Neurosci Biobehav Rev 2010; 34(8):1351–1365.

    Article  PubMed  Google Scholar 

  20. Benjamini Y, Fonio E, Galili T, Havkin GZ, Golani I. Quantifying the build up in extent and complexity of behavior as exemplified in the case of free exploration in mice. Proceedings of the National Academy of Science of the United States 2011. www.pnas.org/cgi/doi/10.1073/pnas.1014837108 Published online before print March 7, 2011, doi: 10.1073/pnas.1014837108 PNAS March 7, 2011.

    Google Scholar 

  21. Fonio E, Benjamini Y, Golani I. Freedom of movement and the stability of its unfolding in free exploration of mice. Proc Natl Acad Sci USA 2009; 106(50):21335–21340.

    Article  PubMed  CAS  Google Scholar 

  22. Lipkind D, Sakov A, Kafkafi N, Elmer GI, Benjamini Y, Golani I. New replicable anxiety-related measures of wall vs center behavior of mice in the open field. J Appl Physiol 2004; 97(1):347–359.

    Article  PubMed  Google Scholar 

  23. von Uexkull J (1957) A Stroll through the worlds of animals and men: A picture book of invisible worlds. Instinctive Behavior: The Development of a Modern Concept, ed Schiller CH (International Univ Press, New York), pp 5–80.

    Google Scholar 

  24. Markou A, Chiamulera C, Geyer MA, Tricklebank M, Steckler T. Removing obstacles in neuroscience drug discovery: the future path for animal models. Neuropsychopharmacology 2009; 34(1):74–89.

    Article  PubMed  CAS  Google Scholar 

  25. Chance MRA. An interpretation of some agonistic postures; the role of “cut-off” acts and postures. Symp Zool Soc London 1962; 8:71–89.

    Google Scholar 

  26. Saper CB. The central autonomic nervous system: conscious visceral perception and autonomic pattern generation. Annu Rev Neurosci 2002; 25:433–469.

    Article  PubMed  CAS  Google Scholar 

  27. Rozanski A, Blumenthal JA, Davidson KW, Saab PG, Kubzansky L. The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology. J Am Coll Cardiol 2005; 45(5):637–651.

    Article  PubMed  Google Scholar 

  28. Koolhaas JM, Meerlo P, De Boer SF, Strubbe JH, Bohus B. The temporal dynamics of the stress response. Neurosci Biobehav Rev 1997; 21(6):775–782.

    Article  PubMed  CAS  Google Scholar 

  29. Stiedl O, Misane I, Koch M, Pattij T, Meyer M, Ögren SO. Activation of the brain 5-HT2C receptors causes hypolocomotion without anxiogenic-like cardiovascular adjustments in mice. Neuropharmacology 2007; 52(3):949–957.

    Article  PubMed  CAS  Google Scholar 

  30. Stiedl O, Youn J, Jansen R. Cardiovascular conditioning: neural substrates. Encyclopedia of Behavioral Neurosciences, Vol. 1. Koob G, Thompson RF & Le Moal M (eds), Elsevier, Amsterdam , 226–235. 1-1-2010.

    Google Scholar 

  31. Stiedl O, Palve M, Radulovic J, Birkenfeld K, Spiess J. Differential impairment of auditory and contextual fear conditioning by protein synthesis inhibition in C57BL/6N mice. Behav Neurosci 1999; 113(3):496–506.

    Article  PubMed  CAS  Google Scholar 

  32. Stiedl O, Spiess J. Effect of tone-dependent fear conditioning on heart rate and behavior of C57BL/6N mice. Behav Neurosci 1997; 111(4):703–711.

    Article  PubMed  CAS  Google Scholar 

  33. Meyer M, Stiedl O. Self-affine fractal variability of human heartbeat interval dynamics in health and disease. Eur J Appl Physiol 2003; 90(3-4):305–316.

    Article  PubMed  CAS  Google Scholar 

  34. Van Erp AM, Kruk MR, Meelis W, Willekens-Bramer DC. Effect of environmental stressors on time course, variability and form of self-grooming in the rat: handling, social contact, defeat, novelty, restraint and fur moistening. Behav Brain Res 1994; 65(1):47–55.

    Article  PubMed  Google Scholar 

  35. Stiedl O, Jansen RF, Pieneman AW, Ögren SO, Meyer M. Assessing aversive emotional states through the heart in mice: implications for cardiovascular dysregulation in affective disorders. Neurosci Biobehav Rev 2009; 33(2):181–190.

    Article  PubMed  CAS  Google Scholar 

  36. Tovote P, Meyer M, Ronnenberg A, Ögren SO, Spiess J, Stiedl O. Heart rate dynamics and behavioral responses during acute emotional challenge in corticotropin-releasing factor receptor 1-deficient and corticotropin-releasing factor-overexpressing mice. Neuroscience 2005; 134(4):1113–1122.

    Article  PubMed  CAS  Google Scholar 

  37. Tovote P, Meyer M, Beck-Sickinger AG, von Hörsten S, Ögren SO, Spiess J et al. Central NPY receptor-mediated alteration of heart rate dynamics in mice during expression of fear conditioned to an auditory cue. Regul Pept 2004; 120(1-3):205–214.

    Article  PubMed  CAS  Google Scholar 

  38. Tovote P, Meyer M, Pilz PK, Ronnenberg A, Ögren SO, Spiess J et al. Dissociation of temporal dynamics of heart rate and blood pressure responses elicited by conditioned fear but not acoustic startle. Behav Neurosci 2005; 119(1):55–65.

    Article  PubMed  Google Scholar 

  39. Stiedl O, Radulovic J, Lohmann R, Birkenfeld K, Palve M, Kammermeier J et al. Strain and substrain differences in context- and tone-dependent fear conditioning of inbred mice. Behav Brain Res 1999; 104(1-2):1–12.

    Article  PubMed  CAS  Google Scholar 

  40. Stiedl O, Tovote P, Ögren SO, Meyer M. Behavioral and autonomic dynamics during contextual fear conditioning in mice. Auton Neurosci 2004; 115(1-2):15–27.

    Article  PubMed  Google Scholar 

  41. Stiedl O, Pieneman AW, Gutzen C, Schwarz S, Jansen RF. Fear conditioning in an automated home cage (DualCage) environment. Proceedings of Measuring Behavior 2010;83–84.

    Google Scholar 

  42. Ögren SO, Stiedl O. Passive avoidance. In: Stolerman IP, editor. Encyclopedia of Psychopharmacology, Vol. 2, Springer, Berlin. 2011: 960–966.

    Google Scholar 

  43. Peng CK, Havlin S, Hausdorff JM, Mietus JE, Stanley HE, Goldberger AL. Fractal mechanisms and heart rate dynamics. Long-range correlations and their breakdown with disease. J Electrocardiol 1995; 28 Suppl:59–65.

    Article  PubMed  Google Scholar 

  44. Meyer M, Marconi C, Ferretti G, Fiocchi R, Cerretelli P, Skinner JE. Heart rate variability in the human transplanted heart: nonlinear dynamics and QT vs RR-QT alterations during exercise suggest a return of neurocardiac regulation in long-term recovery. Integr Physiol Behav Sci 1996; 31(4):289–305.

    Article  PubMed  CAS  Google Scholar 

  45. Ormel J, Petukhova M, Chatterji S, Aguilar-Gaxiola S, Alonso J, Angermeyer MC et al. Disability and treatment of specific mental and physical disorders across the world. Br J Psychiatry 2008; 192(5):368–375.

    Article  PubMed  Google Scholar 

  46. de Mooij-van Malsen AJ, Olivier B, Kas MJ. Behavioural genetics in mood and anxiety: a next step in finding novel pharmacological targets. Eur J Pharmacol 2008; 585(2-3):436–440.

    Google Scholar 

  47. Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003; 160(4):636–645.

    Article  PubMed  Google Scholar 

  48. Kas MJ, Fernandes C, Schalkwyk LC, Collier DA. Genetics of behavioural domains across the neuropsychiatric spectrum; of mice and men. Mol Psychiatry 2007; 12(4):324–330.

    Article  PubMed  CAS  Google Scholar 

  49. Flint J, Valdar W, Shifman S, Mott R. Strategies for mapping and cloning quantitative trait genes in rodents. Nat Rev Genet 2005; 6(4):271–286.

    Article  PubMed  CAS  Google Scholar 

  50. Henderson ND, Turri MG, DeFries JC, Flint J. QTL analysis of multiple behavioral measures of anxiety in mice. Behav Genet 2004; 34(3):267–293.

    Article  PubMed  Google Scholar 

  51. Turri MG, Talbot CJ, Radcliffe RA, Wehner JM, Flint J. High-resolution mapping of quantitative trait loci for emotionality in selected strains of mice. Mamm Genome 1999; 10(11):1098–1101.

    Article  PubMed  CAS  Google Scholar 

  52. Mackay TF. Q&A: Genetic analysis of quantitative traits. J Biol 2009; 8(3):23.

    Article  PubMed  Google Scholar 

  53. Kas MJ, van Ree JM. Dissecting complex behaviours in the post-genomic era. Trends Neurosci 2004; 27(7):366–369.

    Article  PubMed  CAS  Google Scholar 

  54. Singer JB, Hill AE, Burrage LC, Olszens KR, Song J, Justice M et al. Genetic dissection of complex traits with chromosome substitution strains of mice. Science 2004; 304(5669):445–448.

    Article  PubMed  CAS  Google Scholar 

  55. Kas MJ, de Mooij-van Malsen AJ, Olivier B, Spruijt BM, van Ree JM. Differential genetic regulation of motor activity and anxiety-related behaviors in mice using an automated home cage task. Behav Neurosci 2008; 122(4):769–776.

    Google Scholar 

  56. Izidio GS, Spricigo L, Jr., Ramos A. Genetic differences in the elevated plus-maze persist after first exposure of inbred rats to the test apparatus. Behav Processes 2005; 68(2):129–134.

    Article  PubMed  CAS  Google Scholar 

  57. Kas MJ, Gelegen C, Schalkwyk LC, Collier DA. Interspecies comparisons of functional genetic variations and their implications in neuropsychiatry. Am J Med Genet B Neuropsychiatr Genet 2009; 150B(3):309–317.

    Article  PubMed  CAS  Google Scholar 

  58. de Mooij-van Malsen JG, van Lith HA, Oppelaar H, Hendriks J, de Wit M, Kostrzewa E et al. Interspecies trait genetics reveals association of adenylyl cyclase 8 with mouse avoidance behavior and a human mood disorder. Biol Psychiatry 2009; 66: 1123–1130.

    Google Scholar 

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Acknowledgments

OS is thankful to Dr. Christian Gutzen (Biobserve) for his support in adapting the Viewer software for use with external hardware in the automated home cage system.

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Authors and Affiliations

  1. Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands

    Martien J. Kas

  2. Department of Zoology, Tel Aviv University, Tel-Aviv, Israel

    Ilan Golani

  3. Department of Statistics and Operation Research, Tel Aviv University, Tel-Aviv, Israel

    Yoav Benjamini

  4. Department of Neurobiology, Weizmann Institute, Rehovot, Israel

    Ehud Fonio

  5. Center for Neurogenomics and Cognitive Research, VU University Amsterdam, Amsterdam, The Netherlands

    Oliver Stiedl

Authors
  1. Martien J. Kas
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  2. Ilan Golani
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  3. Yoav Benjamini
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  4. Ehud Fonio
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  5. Oliver Stiedl
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Corresponding author

Correspondence to Martien J. Kas .

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Editors and Affiliations

  1. School of Medicine, Department of Psychiatry, University of Maryland, W. Baltimore Street 685, Baltimore, 21201, Maryland, USA

    Todd D. Gould

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Kas, M.J., Golani, I., Benjamini, Y., Fonio, E., Stiedl, O. (2011). Longitudinal Assessment of Deliberate Mouse Behavior in the Home Cage and Attached Environments: Relevance to Anxiety and Mood Disorders. In: Gould, T. (eds) Mood and Anxiety Related Phenotypes in Mice. Neuromethods, vol 63. Humana Press. https://doi.org/10.1007/978-1-61779-313-4_1

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  • DOI: https://doi.org/10.1007/978-1-61779-313-4_1

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-312-7

  • Online ISBN: 978-1-61779-313-4

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