Digging behavior discrimination test to probe burrowing and exploratory digging in male and female mice.

Heather L Pond, Abigail T Heller, Brian M Gural, Olivia P McKissick, Molly K Wilkinson, M Chiara Manzini
Author Information
  1. Heather L Pond: Department of Pharmacology and Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
  2. Abigail T Heller: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Child Health Institute of New Jersey, New Brunswick, NJ, USA.
  3. Brian M Gural: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Child Health Institute of New Jersey, New Brunswick, NJ, USA.
  4. Olivia P McKissick: Department of Pharmacology and Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
  5. Molly K Wilkinson: Department of Pharmacology and Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
  6. M Chiara Manzini: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Child Health Institute of New Jersey, New Brunswick, NJ, USA.

Abstract

Digging behavior is often used to test motor function and repetitive behaviors in mice. Different digging paradigms have been developed for behaviors related to anxiety and compulsion in mouse lines generated to recapitulate genetic mutations leading to psychiatric and neurological disorders. However, the interpretation of these tests has been confounded by the difficulty of determining the motivation behind digging in mice. Digging is a naturalistic mouse behavior that can be focused toward different goals, that is foraging for food, burrowing for shelter, burying objects, or even for recreation as has been shown for dogs, ferrets, and human children. However, the interpretation of results from current testing protocols assumes the motivation behind the behavior often concluding that increased digging is a repetitive or compulsive behavior. We asked whether providing a choice between different types of digging activities would increase sensitivity to assess digging motivation. Here, we present a test to distinguish between burrowing and exploratory digging in mice. We found that mice prefer burrowing when the option is available. When food restriction was used to promote a switch from burrowing to exploration, males readily switched from burrowing to digging outside, while females did not. In addition, when we tested a model of intellectual disability and autism spectrum disorder that had shown inconsistent results in the marble burying test, the Cc2d1a conditional knockout mouse, we found greatly reduced burrowing only in males. Our findings indicate that digging is a nuanced motivated behavior and suggest that male and female rodents may perform it differently.

Keywords

References

  1. Behav Brain Res. 2008 May 16;189(1):126-38 [PMID: 18261809]
  2. Am J Physiol Regul Integr Comp Physiol. 2000 Dec;279(6):R2048-56 [PMID: 11080068]
  3. Psychopharmacology (Berl). 2009 Jun;204(2):361-73 [PMID: 19189082]
  4. Cogn Affect Behav Neurosci. 2019 Feb;19(1):1-39 [PMID: 30361863]
  5. Nat Protoc. 2006;1(1):122-4 [PMID: 17406223]
  6. Behav Brain Res. 2003 Feb 17;139(1-2):139-55 [PMID: 12642185]
  7. Curr Biol. 2017 Dec 18;27(24):3837-3845.e3 [PMID: 29199077]
  8. Behav Pharmacol. 1995 Jan;6(1):24-31 [PMID: 11224308]
  9. Genome Med. 2016 Nov 1;8(1):105 [PMID: 27799067]
  10. Cell. 1996 Dec 27;87(7):1317-26 [PMID: 8980237]
  11. Behav Brain Res. 2005 Jan 30;156(2):241-9 [PMID: 15582110]
  12. Front Behav Neurosci. 2010 Oct 12;4:165 [PMID: 21031028]
  13. J Vis Exp. 2019 Oct 19;(152): [PMID: 31680688]
  14. Endocrinology. 1961 May;68:818-24 [PMID: 13756461]
  15. Biol Psychiatry. 2012 Feb 15;71(4):358-65 [PMID: 21855858]
  16. J Vis Exp. 2012 Jan 05;(59):e2607 [PMID: 22258546]
  17. Behav Pharmacol. 2008 Mar;19(2):145-52 [PMID: 18332679]
  18. Int J Obes Relat Metab Disord. 1999 Apr;23 Suppl 3:S1-6 [PMID: 10367996]
  19. Acta Neurobiol Exp (Wars). 2017;77(3):254-260 [PMID: 29182616]
  20. JAMA Psychiatry. 2017 Mar 1;74(3):293-299 [PMID: 28097321]
  21. J Neurosci. 2010 Dec 1;30(48):16399-407 [PMID: 21123586]
  22. Pharmacology. 2010;86(5-6):293-6 [PMID: 21042039]
  23. Physiol Behav. 2001 Jan;72(1-2):255-62 [PMID: 11240004]
  24. Nat Neurosci. 2015 Oct;18(10):1413-20 [PMID: 26404716]
  25. Cereb Cortex. 2017 Feb 1;27(2):1670-1685 [PMID: 26826102]
  26. Transl Psychiatry. 2019 Sep 9;9(1):222 [PMID: 31501410]
  27. Cell Rep. 2014 Aug 7;8(3):647-55 [PMID: 25066123]
  28. Cell Rep. 2019 Aug 13;28(7):1814-1829.e6 [PMID: 31412249]
  29. Am J Physiol Endocrinol Metab. 2015 Feb 1;308(3):E241-55 [PMID: 25465889]
  30. Behav Brain Res. 2006 Oct 2;173(1):22-9 [PMID: 16870275]
  31. Neuroreport. 2001 Jul 3;12(9):2053-7 [PMID: 11435945]
  32. Endocrinology. 2012 Feb;153(2):949-53 [PMID: 22186416]
  33. Curr Protoc Pharmacol. 2014 Sep 02;66:5.66.1-26 [PMID: 25181011]
  34. Neuropsychol Rev. 2019 Mar;29(1):4-13 [PMID: 31016439]
  35. Eur J Pharmacol. 1986 Jul 31;126(3):223-9 [PMID: 2875886]
  36. J Med Genet. 2006 Mar;43(3):203-10 [PMID: 16033914]
  37. Semin Cell Dev Biol. 2017 Jan;61:107-114 [PMID: 27496333]
  38. J Neurosci Methods. 2014 Aug 30;234:139-46 [PMID: 24525328]
  39. Behav Brain Res. 2007 Jan 10;176(1):27-39 [PMID: 16971001]
  40. Nat Protoc. 2006;1(1):118-21 [PMID: 17406222]
  41. Biochim Biophys Acta Mol Basis Dis. 2020 Oct 1;1866(10):165840 [PMID: 32428559]
  42. Biol Psychiatry. 2019 May 1;85(9):760-768 [PMID: 30732858]
  43. Physiol Behav. 2013 Aug 15;120:156-63 [PMID: 23948671]
  44. J Neurosci. 2019 Jun 19;39(25):4959-4975 [PMID: 30992372]
  45. Behav Brain Res. 2000 Oct;115(1):1-8 [PMID: 10996402]
  46. Pharmacol Biochem Behav. 1996 May;54(1):113-6 [PMID: 8728547]
  47. Front Psychol. 2017 Apr 07;8:456 [PMID: 28439244]
  48. Curr Top Behav Neurosci. 2016;28:1-52 [PMID: 27305922]
  49. Behav Brain Res. 2002 Mar 10;130(1-2):117-25 [PMID: 11864727]
  50. Neurobiol Stress. 2019 Mar 09;10:100155 [PMID: 30949564]
  51. Am J Physiol. 1996 Aug;271(2 Pt 1):E239-45 [PMID: 8770016]
  52. Pharmacol Biochem Behav. 1991 Jan;38(1):63-7 [PMID: 2017455]
  53. J Comp Psychol. 1983 Sep;97(3):249-59 [PMID: 6617152]

Grants

  1. R01 NS105000/NINDS NIH HHS

MeSH Term

Animals
Discrimination Learning
Exploratory Behavior
Female
Food Deprivation
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Sex Characteristics

Word Cloud

Created with Highcharts 10.0.0diggingburrowingbehaviormicetestDiggingrepetitivebehaviorsmousemotivationoftenusedHoweverinterpretationbehinddifferentfoodburyingshownresultsexploratoryfoundmalesmalefemalemotorfunctionDifferentparadigmsdevelopedrelatedanxietycompulsionlinesgeneratedrecapitulategeneticmutationsleadingpsychiatricneurologicaldisorderstestsconfoundeddifficultydeterminingnaturalisticcanfocusedtowardgoalsforagingshelterobjectsevenrecreationdogsferretshumanchildrencurrenttestingprotocolsassumesconcludingincreasedcompulsiveaskedwhetherprovidingchoicetypesactivitiesincreasesensitivityassesspresentdistinguishpreferoptionavailablerestrictionpromoteswitchexplorationreadilyswitchedoutsidefemalesadditiontestedmodelintellectualdisabilityautismspectrumdisorderinconsistentmarbleCc2d1aconditionalknockoutgreatlyreducedfindingsindicatenuancedmotivatedsuggestrodentsmayperformdifferentlydiscriminationprobeRRID:IMSR_CRL:27RRID:IMSR_JAX:005359RRID:IMSR_TAC:b6RRID:MGI:5449582behavioralanalysis

Similar Articles

Cited By (15)