JoVE Logo
Faculty Resource Center

Sign In

Summary

Abstract

Introduction

Protocol

Representative Results

Discussion

Acknowledgements

Materials

References

Behavior

Novel Object Exploration as a Potential Assay for Higher Order Repetitive Behaviors in Mice

Published: August 20th, 2016

DOI:

10.3791/54324

1Department of Biology, University of Redlands

Higher order restricted, repetitive behaviors (RRBs) disrupt the lives of affected individuals. These behaviors are challenging to model in rodents, making basic biomedical research into potential treatments or interventions for RRBs difficult. Here we describe novel object exploration as a potential assay for higher order RRBs in mice.

Restricted, repetitive behaviors (RRBs) are a core feature of autism spectrum disorder (ASD) and disrupt the lives of affected individuals. RRBs are commonly split into lower-order and higher-order components, with lower order RRBs consisting of motor stereotypies and higher order RRBs consisting of perseverative and sequencing behaviors. Higher order RRBs are challenging to model in mice. Current assays for RRBs in mice focus primarily on the lower order components, making basic biomedical research into potential treatments or interventions for higher-order RRBs difficult. Here we describe a new assay, novel object exploration. This assay uses a basic open-field arena with four novel objects placed around the perimeter. The test mouse is allowed to freely explore the arena and the order in which the mouse investigates the novel objects is recorded. From these data, patterned sequences of exploration can be identified, as can the most preferred object for each mouse. The representative data shared here and past results using the novel object exploration assay illustrate that inbred mouse strains do demonstrate different behavior in this assay and that strains with elevated lower order RRBs also show elevated patterned behavior. As such, the novel object exploration assay appears to possess good face validity for higher order RRBs in humans and may be a valuable assay for future studies investigating novel therapeutics for ASD.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder consisting of three core symptoms: social impairment, difficulty communicating through language, and repetitive patterned behaviors1. Since 2000, the number of individuals who have been diagnosed with ASD has increased from 1 in 150 to 1 in 68 in the span of ten years 2. Though the prevalence of the disorder continues to increase, the cause of the disorder is not yet known. There has been a rise in efforts to identify appropriate mouse models for the core and associated symptoms of ASD, as these models could lead to an increased understanding of the underlying symptoms and causes of ....

Log in or to access full content. Learn more about your institution’s access to JoVE content here

The protocol described here was approved by the Institutional Animal Care and Use Committee at the University of Redlands. The C58, C57, and FVB mice used in these studies were bred at the University of Redlands vivarium from stock originally obtained from the Jackson Laboratory (Bar Harbor, ME).  Sentinels from this vivarium were screened every six months and found to be pathogen free.

1. Equipment and Room Set Up

Note: We used two different arenas for novel object testing: a clear plastic rectangu.......

Log in or to access full content. Learn more about your institution’s access to JoVE content here

The representative data22 show that female C58/J mice displayed a higher number of sequenced patterns than the other strains in the round arena (Figure 2, panel A), but not in the rectangular arena (Figure 2, panel C). None of the three male strains differed from each other (Figure 2, panels B and D). The representative data show that both male and female C58/J mice display a stronger preference for their most visited object (a.......

Log in or to access full content. Learn more about your institution’s access to JoVE content here

Here, we present a recently developed assay that may be useful for quantifying mouse behaviors with face validity for higher order repetitive behaviors in humans. Unlike more established assays like the Barnes or T-maze, this novel object exploration assay does not require any mouse training nor is it particularly anxiety provoking. Additionally, novel object exploration does not require any food or social stimuli, allowing for more focus on the behaviors of interest, RRBs, and decreasing the likelihood of confounding va.......

Log in or to access full content. Learn more about your institution’s access to JoVE content here

The authors would like to acknowledge the Summer Undergraduate Research Program, the Academic Technology User Group, the Center for Digital Learning, and the Science Center at the University of Redlands.

The authors would like to dedicate this paper to the memory of Lou Yango.

....

Log in or to access full content. Learn more about your institution’s access to JoVE content here

Name Company Catalog Number Comments
Standard Polycarbonate Rodent Cage (45 x 24 x 20 cm) Multiple cages are desirable to facilitate testing of multiple mice 
Plastic Opaque Circular Testing Arena (41 cm base diameter) United States Plastic Corp. 13931 Multiple arenas are desirable to facilitate testing of multiple mice 
Standard Corn-Cob Rodent Bedding
Novel Object - red monkey Hasbro, Pawtucket RI from Barrel of Monkeys
Novel Object - rectangular 2x4 LEGO
Novel Object - tile Thinkfun Inc., Alexandria VA from Toot and Otto
Novel Object - standard white die
Video Camera
Behavioral Logging Software - The Observer Noldus, Wageningen, The Netherlands other programs may be used
Video Tracking Software - EthoVision Noldus, Wageningen, The Netherlands other programs may be used
X-Keys input keyboard P.I. Engineering, Williamstown MI 829484
MacroWorks II P.I. Engineering, Williamstown MI

  1. American Psychological Association. . Diagnostic and Statistical Manual of Mental Disorders. , (2013).
  2. Baio, J. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States. Morb. Mortal. Wkly. Rep. 63 (SS02), 1-21 (2010).
  3. Moy, S. S., et al. Social approach and repetitive behavior in eleven inbred mouse strains. Behav. Brain Res. 191 (1), 118-129 (2008).
  4. Bodfish, J. W., Symons, F. J., Parker, D. E., Lewis, M. H. Varieties of repetitive behavior in autism: comparisons to mental retardation. J. Autism Dev. Disord. 30 (3), 237-243 (2000).
  5. Lewis, M. H., Kim, S. The pathophysiology of restricted repetitive behavior. J. Neurodev. Disord. 1 (2), 114-132 (2009).
  6. Lewis, M. H., Bodfish, J. W. Repetitive behavior disorders in autism. Ment. Retard. Dev. Disabil. Res. Rev. 4, 80-89 (1998).
  7. Lam, K. S. L., Bodfish, J. W., Piven, J. Evidence for three subtypes of repetitive behavior in autism that differ in familiarity and association with other symptoms. J. Child Psychol. Psychiatry. 49 (11), 1193-1200 (2008).
  8. Bishop, S. L., et al. Subcategories of Restricted and Repetitive Behaviors in Children with Autism Spectrum Disorders. J. Autism Dev. Disord. 43 (6), 1287-1297 (2013).
  9. Lewis, M. H., Tanimura, Y., Lee, L. W., Bodfish, J. W. Animal models of restricted repetitive behavior in autism. Behav. Brain Res. 176 (1), 66-74 (2007).
  10. Korff, S., Stein, D. J., Harvey, B. H. Stereotypic behaviour in the deer mouse: Pharmacological validation and relevance for obsessive compulsive disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry. 32 (2), 348-355 (2008).
  11. Ryan, B. C., Young, N. B., Crawley, J. N., Bodfish, J. W., Moy, S. S. Social deficits, stereotypy and early emergence of repetitive behavior in the C58/J inbred mouse strain. Behav. Brain Res. 206 (1), 178-188 (2010).
  12. Moy, S. S., et al. Mouse behavioral tasks relevant to autism: phenotypes of 10 inbred strains. Behav. Brain Res. 176, 4-20 (2007).
  13. Moy, S. S., Nadler, J. J., Poe, M. D., Nonneman, R. J., Young, N. B., Koller, B. H., et al. Development of a mouse test for repetitive, restricted behaviors: relevance to autism. Behav. Brain Res. 188 (1), 178-194 (2008).
  14. Moy, S. S., et al. Repetitive behavior profile and supersensitivity to amphetamine in the C58/J mouse model of autism. Behav. Brain Res. 259, 200-214 (2014).
  15. Scattoni, M. L., Gandhy, S. U., Ricceri, L., Crawley, J. N. Unusual repertoire of vocalizations in the BTBR T+tf/J mouse model of autism. PLoS ONE. 3 (8), e3067 (2008).
  16. Muehlmann, A. M., et al. Further characterization of repetitive behavior in C58 mice: developmental trajectory and effects of environmental enrichment. Behav. Brain Res. 235, 143-149 (2012).
  17. Pearson, B. L., et al. Motor and cognitive stereotypies in the BTBR T+tf/J mouse model of autism. Genes Brain Behav. 10 (2), 228-235 (2011).
  18. Belzung, C., Crusio, W. E., Gerlai, R. T. Measuring exploratory behavior. Handbook of molecular genetic techniques for brain and behavior research (techniques in the behavioral and neural sciences). , 739-749 (1999).
  19. Kalueff, A. V., Keisala, T., Minasyan, A., Kuuslahti, M., Tuohimaa, P. Temporal stability of novelty exploration in mice exposed to different open field tests. Behav. Process. 72, 104-112 (2006).
  20. Prut, L., Belzung, C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur. J. Pharmacol. 46, 3-33 (2003).
  21. Walsh, R. N., Cumins, R. A. The open-field test: a critical review. Psychol. Bull. 83 (3), 482-504 (1976).
  22. Blick, M. G., Puchalski, B. H., Bolanos, V. J., Wolfe, K. M., Green, M. C., Ryan, B. C. Novel object exploration in the C58/J mouse model of autistic-like behavior. Behav. Brain Res. 282, 54-60 (2015).
  23. Crawley, J. N., et al. Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies. Psychopharmacol. 132, 107-124 (1997).
  24. Logue, S. F., Owen, E. H., Rasmussen, D. L., Wehner, J. M. Assessment of locomotor activity, acoustic and tactile startle and prepulse inhibition of startle in inbred mouse strains and F1 hybrids: implications of genetic background for single gene and quantitative trait loci analyses. Neurosci. 80 (4), 1075-1086 (1997).
  25. Lamprea, M. R., Cardenas, F. P., Setem, J., Morato, S. Thigmotactic responses in an open-field. Braz. J. Med. Biol. Res. 41, 135-140 (2008).

This article has been published

Video Coming Soon

JoVE Logo

Privacy

Terms of Use

Policies

Research

Education

ABOUT JoVE

Copyright © 2024 MyJoVE Corporation. All rights reserved