Automated Three‐Chambered Social Approach Task for Mice

Autism is diagnosed by three major symptom categories: unusual reciprocal social interactions, impaired communication, and repetitive behaviors with restricted interests. Direct social approach in mice has strong face validity to simple social approach behaviors in humans, which are frequently impaired in autism. This unit presents a basic protocol for a standardized, high‐throughput social approach test for assaying mouse sociability. Our automated three‐chambered social approach task quantifies direct social approach behaviors when a subject mouse is presented with the choice of spending time with either a novel mouse or a novel object. Sociability is defined as the subject mouse spending more time in the chamber containing the novel target mouse than in the chamber containing the inanimate novel object. The Basic Protocol describes procedures for testing one subject at a time in a single apparatus. A Support Protocol addresses data collection. Curr. Protoc. Neurosci. 56:8.26.1‐8.26.16. © 2011 by John Wiley & Sons, Inc.

[1]  J. Crawley,et al.  Olfactory cues are sufficient to elicit social approach behaviors but not social transmission of food preference in C57BL/6J mice , 2008, Behavioural Brain Research.

[2]  Jacqueline N. Crawley,et al.  Development of a mouse test for repetitive, restricted behaviors: Relevance to autism , 2008, Behavioural Brain Research.

[3]  Jill L Silverman,et al.  Repetitive Self-Grooming Behavior in the BTBR Mouse Model of Autism is Blocked by the mGluR5 Antagonist MPEP , 2010, Neuropsychopharmacology.

[4]  Kathryn K. Chadman,et al.  Fluoxetine but not risperidone increases sociability in the BTBR mouse model of autism , 2011, Pharmacology Biochemistry and Behavior.

[5]  R. Hevner,et al.  Multiple autism-like behaviors in a novel transgenic mouse model , 2011, Behavioural Brain Research.

[6]  Jack W. Tsao,et al.  What's wrong with my mouse: Behavioral phenotyping of transgenic and knockout mice, J. Crawley. Wiley-Interscience, Hoboken, NJ (2007), 523 pages, $99.95 , 2008 .

[7]  J. Crawley,et al.  Behavioral Phenotyping Strategies for Mutant Mice , 2008, Neuron.

[8]  J. Crawley.  Mouse Behavioral Assays Relevant to the Symptoms of Autism * , 2007, Brain pathology.

[9]  Jacqueline N. Crawley,et al.  Social deficits in BTBR T + tf/J mice are unchanged by cross-fostering with C57BL/6J mothers , 2007, International Journal of Developmental Neuroscience.

[10]  J. Winslow,et al.  Mouse Social Recognition and Preference , 2003, Current protocols in neuroscience.

[11]  J. Piven,et al.  Sociability and preference for social novelty in five inbred strains: an approach to assess autistic‐like behavior in mice , 2004, Genes, brain, and behavior.

[12]  H. McFarlane,et al.  Autism‐like behavioral phenotypes in BTBR T+tf/J mice , 2008, Genes, brain, and behavior.

[13]  D. Blanchard,et al.  A new test paradigm for social recognition evidenced by urinary scent marking behavior in C57BL/6J mice , 2008, Behavioural Brain Research.

[14]  S S Moy,et al.  Social approach in genetically engineered mouse lines relevant to autism , 2009, Genes, brain, and behavior.

[15]  R. Beynon,et al.  Individual recognition in mice mediated by major urinary proteins , 2001, Nature.

[16]  J. Frahm,et al.  Neuroligin‐3‐deficient mice: model of a monogenic heritable form of autism with an olfactory deficit , 2009, Genes, brain, and behavior.

[17]  J. Crawley,et al.  Postnatal lesion evidence against a primary role for the corpus callosum in mouse sociability , 2009, The European journal of neuroscience.

[18]  J. Roder,et al.  Assessment of Social Interaction Behaviors , 2011, Journal of visualized experiments : JoVE.

[19]  Shiaoching Gong,et al.  Minimal aberrant behavioral phenotypes of neuroligin‐3 R451C knockin mice , 2008, Autism research : official journal of the International Society for Autism Research.

[20]  Jacqueline N. Crawley,et al.  Social approach behaviors in oxytocin knockout mice: Comparison of two independent lines tested in different laboratory environments , 2007, Neuropeptides.

[21]  Todd H. Ahern,et al.  Evaluation of two automated metrics for analyzing partner preference tests , 2009, Journal of Neuroscience Methods.

[22]  R. Rodgers,et al.  Contrasting phenotypes of C57BL/6JOlaHsd, 129S2/SvHsd and 129/SvEv mice in two exploration-based tests of anxiety-related behaviour , 2002, Physiology & Behavior.

[23]  Wei Zhang,et al.  Pharmacological Inhibition of mTORC1 Suppresses Anatomical, Cellular, and Behavioral Abnormalities in Neural-Specific Pten Knock-Out Mice , 2009, The Journal of Neuroscience.

[24]  Enrico Alleva,et al.  Ultrasonic vocalisation emitted by infant rodents: a tool for assessment of neurobehavioural development , 2001, Behavioural Brain Research.

[25]  Jacqueline N. Crawley,et al.  Mouse behavioral tasks relevant to autism: Phenotypes of 10 inbred strains , 2007, Behavioural Brain Research.

[26]  Jacqueline N. Crawley,et al.  Sociability and motor functions in Shank1 mutant mice , 2011, Brain Research.

[27]  J. Lieberman,et al.  Deficits in sensorimotor gating and tests of social behavior in a genetic model of reduced NMDA receptor function , 2004, Behavioural Brain Research.

[28]  C. Lord,et al.  Behavioural phenotyping assays for mouse models of autism , 2010, Nature Reviews Neuroscience.

[29]  Valerie J. Bolivar,et al.  A novel social proximity test suggests patterns of social avoidance and gaze aversion-like behavior in BTBR T+ tf/J mice , 2011, Behavioural Brain Research.

[30]  Valerie J. Bolivar,et al.  Assessing autism-like behavior in mice: Variations in social interactions among inbred strains , 2007, Behavioural Brain Research.

[31]  D. B. Bell,et al.  Low stress reactivity and neuroendocrine factors in the BTBR T+tf/J mouse model of autism , 2010, Neuroscience.

[32]  D. Murphy,et al.  Abnormal anxiety‐related behavior in serotonin transporter null mutant mice: the influence of genetic background , 2003, Genes, brain, and behavior.

[33]  J. Crawley,et al.  Social peers rescue autism‐relevant sociability deficits in adolescent mice , 2011, Autism research : official journal of the International Society for Autism Research.

[34]  C. Lord,et al.  Autism from 2 to 9 years of age. , 2006, Archives of general psychiatry.

[35]  M. Sur,et al.  Haploinsufficiency for Pten and Serotonin transporter cooperatively influences brain size and social behavior , 2009, Proceedings of the National Academy of Sciences.

[36]  R. Nonneman,et al.  Social approach and repetitive behavior in eleven inbred mouse strains , 2008, Behavioural Brain Research.

[37]  Hewlet G McFarlane,et al.  Social Approach Behaviors are Similar on Conventional Versus Reverse Lighting Cycles, and in Replications Across Cohorts, in BTBR T+ tf/J, C57BL/6J, and Vasopressin Receptor 1B Mutant Mice , 2007, Frontiers in behavioral neuroscience.

[38]  Alcino J. Silva,et al.  Neuronal Glucose Transporter Isoform 3 Deficient Mice Demonstrate Features of Autism Spectrum Disorders , 2009, Molecular Psychiatry.

[39]  Timothy M. DeLorey,et al.  Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar vermal lobules: A potential model of autism spectrum disorder , 2008, Behavioural Brain Research.

[40]  G. Laviola,et al.  The developmental psychobiology of behavioural plasticity in mice: the role of social experiences in the family unit , 1998, Neuroscience & Biobehavioral Reviews.

[41]  Jacqueline N. Crawley,et al.  What's Wrong With My Mouse? , 2007 .

[42]  K. Miczek,et al.  Aggressive behavioral phenotypes in mice , 2001, Behavioural Brain Research.

[43]  J. Ostrem,et al.  Differential effects of prior dominance or subordination experience on conspecific odor preferences in mice , 1993, Physiology & Behavior.

[44]  Garet P Lahvis,et al.  Social reward among juvenile mice , 2007, Genes, brain, and behavior.

[45]  Garet P. Lahvis,et al.  Affiliative Behavior, Ultrasonic Communication and Social Reward Are Influenced by Genetic Variation in Adolescent Mice , 2007, PloS one.

[46]  Jens Frahm,et al.  Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism , 2008, Proceedings of the National Academy of Sciences.

[47]  T. Miyakawa,et al.  Comprehensive Behavioral Phenotyping of Ryanodine Receptor type 3 (RyR3) Knockout Mice: Decreased Social Contact Duration in Two Social Interaction Tests , 2009, Front. Behav. Neurosci..

[48]  A. Moles,et al.  Ultrasonic vocalization by female mice in the presence of a conspecific carrying food cues , 2000, Animal Behaviour.

[49]  Lee M. Silver,et al.  Social approach–avoidance behavior of inbred mouse strains towards DBA/2 mice , 2004, Brain Research.

[50]  Catherine Lord,et al.  The autism spectrum: definitions, assessment and diagnoses. , 2009, British journal of hospital medicine.

[51]  J. Piven,et al.  Automated apparatus for quantitation of social approach behaviors in mice , 2004, Genes, brain, and behavior.

[52]  V. Bouet,et al.  Effect of pre- versus post-weaning environmental disturbances on social behaviour in mice , 2011, Neuroscience Letters.

[53]  D. Pfaff,et al.  Inadvertent social information and the avoidance of parasitized male mice: a role for oxytocin. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[54]  Kiyoshi Inoue,et al.  Abnormal Behavior in a Chromosome- Engineered Mouse Model for Human 15q11-13 Duplication Seen in Autism , 2009, Cell.

[55]  J. Crawley.  Designing mouse behavioral tasks relevant to autistic-like behaviors. , 2004, Mental retardation and developmental disabilities research reviews.

[56]  Alexandre Reymond,et al.  Abnormal social behaviors and altered gene expression rates in a mouse model for Potocki-Lupski syndrome. , 2008, Human molecular genetics.

[57]  S. Tobet,et al.  Adolescent social isolation changes social recognition in adult mice , 2011, Behavioural Brain Research.

[58]  T. Nabeshima,et al.  Behavioral abnormality and pharmacologic response in social isolation-reared mice , 2009, Behavioural Brain Research.

[59]  F. D'Amato,et al.  Mother-offspring interaction and pup development in genetically deaf mice , 1987, Behavior genetics.

[60]  A. Ayadi,et al.  Mouse Breeding and Colony Management. , 2011, Current protocols in mouse biology.