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Published in: Molecular Autism 1/2017

Open Access 01-12-2017 | Methodology

A novel system for tracking social preference dynamics in mice reveals sex- and strain-specific characteristics

Authors: Shai Netser, Shani Haskal, Hen Magalnik, Shlomo Wagner

Published in: Molecular Autism | Issue 1/2017

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Abstract

Background

Deciphering the biological mechanisms underlying social behavior in animal models requires standard behavioral paradigms that can be unbiasedly employed in an observer- and laboratory-independent manner. During the past decade, the three-chamber test has become such a standard paradigm used to evaluate social preference (sociability) and social novelty preference in mice. This test suffers from several caveats, including its reliance on spatial navigation skills and negligence of behavioral dynamics.

Methods

Here, we present a novel experimental apparatus and an automated analysis system which offer an alternative to the three-chamber test while solving the aforementioned caveats. The custom-made apparatus is simple for production, and the analysis system is publically available as an open-source software, enabling its free use. We used this system to compare the dynamics of social behavior during the social preference and social novelty preference tests between male and female C57BL/6J mice.

Results

We found that in both tests, male mice keep their preference towards one of the stimuli for longer periods than females. We then employed our system to define several new parameters of social behavioral dynamics in mice and revealed that social preference behavior is segregated in time into two distinct phases. An early exploration phase, characterized by high rate of transitions between stimuli and short bouts of stimulus investigation, is followed by an interaction phase with low transition rate and prolonged interactions, mainly with the preferred stimulus. Finally, we compared the dynamics of social behavior between C57BL/6J and BTBR male mice, the latter of which are considered as asocial strain serving as a model for autism spectrum disorder. We found that BTBR mice (n = 8) showed a specific deficit in transition from the exploration phase to the interaction phase in the social preference test, suggesting a reduced tendency towards social interaction.

Conclusions

We successfully employed our new experimental system to unravel previously unidentified sex- and strain-specific differences in the dynamics of social behavior in mice. Thus, the system presented here facilitates a more thorough and detailed analysis of social behavior in small rodent models, enabling a better comparison between strains and treatments.
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Literature
1.
go back to reference Insel TR. The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior. Neuron. 2010;65(6):768–79.CrossRefPubMedPubMedCentral Insel TR. The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior. Neuron. 2010;65(6):768–79.CrossRefPubMedPubMedCentral
2.
go back to reference Moy SS, Nadler JJ, Perez A, Barbaro RP, Johns JM, Magnuson TR, Piven J, Crawley JN. Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behavior in mice. Genes Brain Behav. 2004;3(5):287–302.CrossRefPubMed Moy SS, Nadler JJ, Perez A, Barbaro RP, Johns JM, Magnuson TR, Piven J, Crawley JN. Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behavior in mice. Genes Brain Behav. 2004;3(5):287–302.CrossRefPubMed
3.
go back to reference Carr WJ, Yee L, Gable D, Marasco E. Olfactory recognition of conspecifics by domestic Norway rats. J Comp Physiol Psychol. 1976;90(9):821–8.CrossRefPubMed Carr WJ, Yee L, Gable D, Marasco E. Olfactory recognition of conspecifics by domestic Norway rats. J Comp Physiol Psychol. 1976;90(9):821–8.CrossRefPubMed
4.
go back to reference Ferguson JN, Aldag JM, Insel TR, Young LJ. Oxytocin in the medial amygdala is essential for social recognition in the mouse. J Neurosci. 2001;21(20):8278–85.PubMed Ferguson JN, Aldag JM, Insel TR, Young LJ. Oxytocin in the medial amygdala is essential for social recognition in the mouse. J Neurosci. 2001;21(20):8278–85.PubMed
5.
go back to reference 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(2):152–63.CrossRefPubMed 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(2):152–63.CrossRefPubMed
6.
go back to reference Kazdoba TM, Leach PT, Yang M, Silverman JL, Solomon M, Crawley JN. Translational mouse models of autism: advancing toward pharmacological therapeutics. Curr Top Behav Neurosci. 2016;28:1–52.PubMedPubMedCentral Kazdoba TM, Leach PT, Yang M, Silverman JL, Solomon M, Crawley JN. Translational mouse models of autism: advancing toward pharmacological therapeutics. Curr Top Behav Neurosci. 2016;28:1–52.PubMedPubMedCentral
7.
go back to reference Moy SS, Nadler JJ. Advances in behavioral genetics: mouse models of autism. Mol Psychiatry. 2008;13(1):4–26.CrossRefPubMed Moy SS, Nadler JJ. Advances in behavioral genetics: mouse models of autism. Mol Psychiatry. 2008;13(1):4–26.CrossRefPubMed
8.
go back to reference Moy SS, Nadler JJ, Magnuson TR, Crawley JN. Mouse models of autism spectrum disorders: the challenge for behavioral genetics. Am J Med Genet C: Semin Med Genet. 2006;142C(1):40–51.CrossRef Moy SS, Nadler JJ, Magnuson TR, Crawley JN. Mouse models of autism spectrum disorders: the challenge for behavioral genetics. Am J Med Genet C: Semin Med Genet. 2006;142C(1):40–51.CrossRef
9.
go back to reference Wohr M, Scattoni ML. Behavioural methods used in rodent models of autism spectrum disorders: current standards and new developments. Behav Brain Res. 2013;251:5–17.CrossRefPubMed Wohr M, Scattoni ML. Behavioural methods used in rodent models of autism spectrum disorders: current standards and new developments. Behav Brain Res. 2013;251:5–17.CrossRefPubMed
11.
go back to reference Goodson JL. Deconstructing sociality, social evolution and relevant nonapeptide functions. Psychoneuroendocrinology. 2013;38(4):465–78.CrossRefPubMed Goodson JL. Deconstructing sociality, social evolution and relevant nonapeptide functions. Psychoneuroendocrinology. 2013;38(4):465–78.CrossRefPubMed
12.
go back to reference Zilkha N, Sofer Y, Beny Y, Kimchi T. From classic ethology to modern neuroethology: overcoming the three biases in social behavior research. Curr Opin Neurobiol. 2016;38:96–108.CrossRefPubMed Zilkha N, Sofer Y, Beny Y, Kimchi T. From classic ethology to modern neuroethology: overcoming the three biases in social behavior research. Curr Opin Neurobiol. 2016;38:96–108.CrossRefPubMed
13.
go back to reference Moy SS, Nadler JJ, Young NB, Perez A, Holloway LP, Barbaro RP, Barbaro JR, Wilson LM, Threadgill DW, Lauder JM, et al. Mouse behavioral tasks relevant to autism: phenotypes of 10 inbred strains. Behav Brain Res. 2007;176(1):4–20.CrossRefPubMed Moy SS, Nadler JJ, Young NB, Perez A, Holloway LP, Barbaro RP, Barbaro JR, Wilson LM, Threadgill DW, Lauder JM, et al. Mouse behavioral tasks relevant to autism: phenotypes of 10 inbred strains. Behav Brain Res. 2007;176(1):4–20.CrossRefPubMed
14.
go back to reference Crawley JN. Mouse behavioral assays relevant to the symptoms of autism. Brain Pathol. 2007;17(4):448–59.CrossRefPubMed Crawley JN. Mouse behavioral assays relevant to the symptoms of autism. Brain Pathol. 2007;17(4):448–59.CrossRefPubMed
15.
16.
go back to reference Nadler JJ, Moy SS, Dold G, Trang D, Simmons N, Perez A, Young NB, Barbaro RP, Piven J, Magnuson TR, et al. Automated apparatus for quantitation of social approach behaviors in mice. Genes Brain Behav. 2004;3(5):303–14.CrossRefPubMed Nadler JJ, Moy SS, Dold G, Trang D, Simmons N, Perez A, Young NB, Barbaro RP, Piven J, Magnuson TR, et al. Automated apparatus for quantitation of social approach behaviors in mice. Genes Brain Behav. 2004;3(5):303–14.CrossRefPubMed
18.
go back to reference Matthews GA, Nieh EH, Vander Weele CM, Halbert SA, Pradhan RV, Yosafat AS, Glober GF, Izadmehr EM, Thomas RE, Lacy GD, et al. Dorsal raphe dopamine neurons represent the experience of social isolation. Cell. 2016;164(4):617–31.CrossRefPubMedPubMedCentral Matthews GA, Nieh EH, Vander Weele CM, Halbert SA, Pradhan RV, Yosafat AS, Glober GF, Izadmehr EM, Thomas RE, Lacy GD, et al. Dorsal raphe dopamine neurons represent the experience of social isolation. Cell. 2016;164(4):617–31.CrossRefPubMedPubMedCentral
19.
go back to reference Yang M, Bozdagi O, Scattoni ML, Wohr M, Roullet FI, Katz AM, Abrams DN, Kalikhman D, Simon H, Woldeyohannes L, et al. Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice. J Neurosci. 2012;32(19):6525–41.CrossRefPubMedPubMedCentral Yang M, Bozdagi O, Scattoni ML, Wohr M, Roullet FI, Katz AM, Abrams DN, Kalikhman D, Simon H, Woldeyohannes L, et al. Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice. J Neurosci. 2012;32(19):6525–41.CrossRefPubMedPubMedCentral
20.
go back to reference Hong W, Kennedy A, Burgos-Artizzu XP, Zelikowsky M, Navonne SG, Perona P, Anderson DJ. Automated measurement of mouse social behaviors using depth sensing, video tracking, and machine learning. Proc Natl Acad Sci U S A. 2015;112(38):E5351–60.CrossRefPubMedPubMedCentral Hong W, Kennedy A, Burgos-Artizzu XP, Zelikowsky M, Navonne SG, Perona P, Anderson DJ. Automated measurement of mouse social behaviors using depth sensing, video tracking, and machine learning. Proc Natl Acad Sci U S A. 2015;112(38):E5351–60.CrossRefPubMedPubMedCentral
21.
go back to reference Krueger-Burg D, Winkler D, Mitkovski M, Daher F, Ronnenberg A, Schluter OM, Dere E, Ehrenreich H. The SocioBox: a novel paradigm to assess complex social recognition in male mice. Front Behav Neurosci. 2016;10:151.CrossRefPubMedPubMedCentral Krueger-Burg D, Winkler D, Mitkovski M, Daher F, Ronnenberg A, Schluter OM, Dere E, Ehrenreich H. The SocioBox: a novel paradigm to assess complex social recognition in male mice. Front Behav Neurosci. 2016;10:151.CrossRefPubMedPubMedCentral
Metadata
Title
A novel system for tracking social preference dynamics in mice reveals sex- and strain-specific characteristics
Authors
Shai Netser
Shani Haskal
Hen Magalnik
Shlomo Wagner
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2017
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-017-0169-1

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