Assessing autism-like behavior in mice: Variations in social interactions among inbred strains

Bolivar, Valerie J.; Walters, Samantha R.; Phoenix, Jennifer L.

doi:10.1016/j.bbr.2006.09.007

Cited by 234 publications

(253 citation statements)

References 53 publications

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“…By using our behavioral analysis system to track the locations, poses, and behaviors of the interacting animals, we observed significantly less social investigation performed by BTBR animals in comparison with C57BL/6N controls ( Fig. 6 A-C), consistent with previous reports (38,39). In particular, the BTBR animals displayed shorter bouts of (Fig.…”

Section: Resultssupporting

confidence: 89%

“…We show that tracking analysis alone was incapable of detecting differences in the frequency of social interactions between control C57BL/6N mice and BTBR mice, a previously reported autism model (1,(37)(38)(39). Application of the pose estimator, by contrast, detected a significant difference between strains, as did the automated behavior classifier.…”

Section: Discussionmentioning

confidence: 77%

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Automated measurement of mouse social behaviors using depth sensing, video tracking, and machine learning

Hong

Kennedy

Burgos-Artizzu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

263

234

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A lack of automated, quantitative, and accurate assessment of social behaviors in mammalian animal models has limited progress toward understanding mechanisms underlying social interactions and their disorders such as autism. Here we present a new integrated hardware and software system that combines video tracking, depth sensing, and machine learning for automatic detection and quantification of social behaviors involving close and dynamic interactions between two mice of different coat colors in their home cage. We designed a hardware setup that integrates traditional video cameras with a depth camera, developed computer vision tools to extract the body "pose" of individual animals in a social context, and used a supervised learning algorithm to classify several well-described social behaviors. We validated the robustness of the automated classifiers in various experimental settings and used them to examine how genetic background, such as that of Black and Tan Brachyury (BTBR) mice (a previously reported autism model), influences social behavior. Our integrated approach allows for rapid, automated measurement of social behaviors across diverse experimental designs and also affords the ability to develop new, objective behavioral metrics.

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Section: Resultssupporting

confidence: 89%

Section: Discussionmentioning

confidence: 77%

Automated measurement of mouse social behaviors using depth sensing, video tracking, and machine learning

Hong

Kennedy

Burgos-Artizzu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

263

234

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“…In basic research, few animal models for autism are available, and most studies include only male animals, as the disorder is more prevalent in males (Bolivar et al, 2007;McFarlane et al, 2008;Karvat and Kimchi, 2012;Oddi et al, 2013) (Table 8). One such model is based on the prenatal exposure of rats to the antiepileptic drug valproic acid.…”

Section: Sex Differences In Animal Models Of Autismmentioning

confidence: 99%

“…These patients frequently present other symptoms, such as anxiety, aberrant sensitivity to sensory stimulation and immunological disorders. Autism is much higher in boys than in girls with a ratio of 4:1 (Fombonne, 2003).In basic research, few animal models for autism are available, and most studies include only male animals, as the disorder is more prevalent in males (Bolivar et al, 2007;McFarlane et al, 2008;Karvat and Kimchi, 2012;Oddi et al, 2013) (Table 8). One such model is based on the prenatal exposure of rats to the antiepileptic drug valproic acid.…”

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confidence: 99%

Sex differences in animal models of psychiatric disorders

Kokras

Dalla

2014

British J Pharmacology

339

187

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Psychiatric disorders are characterized by sex differences in their prevalence, symptomatology and treatment response. Animal models have been widely employed for the investigation of the neurobiology of such disorders and the discovery of new treatments. However, mostly male animals have been used in preclinical pharmacological studies. In this review, we highlight the need for the inclusion of both male and female animals in experimental studies aiming at gender-oriented prevention, diagnosis and treatment of psychiatric disorders. We present behavioural findings on sex differences from animal models of depression, anxiety, post-traumatic stress disorder, substance-related disorders, obsessive-compulsive disorder, schizophrenia, bipolar disorder and autism. Moreover, when available, we include studies conducted across different stages of the oestrous cycle. By inspection of the relevant literature, it is obvious that robust sex differences exist in models of all psychiatric disorders. However, many times results are conflicting, and no clear conclusion regarding the direction of sex differences and the effect of the oestrous cycle is drawn. Moreover, there is a lack of considerable amount of studies using psychiatric drugs in both male and female animals, in order to evaluate the differential response between the two sexes. Notably, while in most cases animal models successfully mimic drug response in both sexes, test parameters and treatment-sensitive behavioural indices are not always the same for male and female rodents. Thus, there is an increasing need to validate animal models for both sexes and use standard procedures across different laboratories. LINKED ARTICLESThis article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10. 1111/bph.2014.171.issue-20 Abbreviations 5-HTT, 5-HT transporter; 8-OH-DPAT, 7-(Dipropylamino)-5,6,7,8-tetrahydronaphthalen-1-ol; Akt1, V-akt murine thymoma viral oncogene homologue 1; BDNF, brain-derived neurotrophic factor; BTBR, BTBR T + tf/J; CMS, chronic mild stress; COMT, catechol-O-methyltransferase-deficient mice; CR, conditioned response; CRF, corticotrophinreleasing factor; CS, conditioned stimulus; D1 receptor, dopamine 1 receptor; D2 receptor, dopamine 2 receptor; DISC1, disrupted-in-schizophrenia 1; Ehmt1, euchromatin histone methyltransferase 1; FBGRKO, forebrain glucocorticoid type II receptor (NR3C1) knockout; FSL, flinders sensitive rat line; FST, forced swim test; GSK3, glycogen synthase kinase 3; HAB, high anxiety-related behaviour rats; ICSS, intracranial self-stimulation; LAB, low anxiety-related behaviour rats; LI, latent inhibition; Mthfr, methylenetetrahydrofolate reductase; OCD, obsessive-compulsive disorder; PPI, prepulse inhibition; PTSD, post-traumatic stress disorder; SSRI, selective 5-HT re-uptake inhibitors; US, unconditioned stimulus; WKY, Wistar Kyoto IntroductionThe total disease burden for neuropsychiatric disorders in the European Union has been recently ...

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“…[17][18][19] Overall, inbred strain phenotypes vary across a continuum of social behavior, with extremes of high social preference and overt social avoidance. 17,[20][21][22] The symptom of repetitive behavior encompasses both 'lower-order' motoric stereotypy and self-injury, and 'higher-order' responses reflecting general cognitive rigidity, such as restricted, obsessive interests and strong resistance to environmental change. 13,23,24 Both components of the repetitive behavior domain tend to co-occur in children with autism or related disorders.…”

Section: Behavioral Phenotyping Of Mouse Modelsmentioning

confidence: 99%

Advances in behavioral genetics: mouse models of autism

2007

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Autism is a neurodevelopmental syndrome with markedly high heritability. The diagnostic indicators of autism are core behavioral symptoms, rather than definitive neuropathological markers. Etiology is thought to involve complex, multigenic interactions and possible environmental contributions. In this review, we focus on genetic pathways with multiple members represented in autism candidate gene lists. Many of these pathways can also be impinged upon by environmental risk factors associated with the disorder. The mouse model system provides a method to experimentally manipulate candidate genes for autism susceptibility, and to use environmental challenges to drive aberrant gene expression and cell pathology early in development. Mouse models for fragile X syndrome, Rett syndrome and other disorders associated with autistic-like behavior have elucidated neuropathology that might underlie the autism phenotype, including abnormalities in synaptic plasticity. Mouse models have also been used to investigate the effects of alterations in signaling pathways on neuronal migration, neurotransmission and brain anatomy, relevant to findings in autistic populations. Advances have included the evaluation of mouse models with behavioral assays designed to reflect disease symptoms, including impaired social interaction, communication deficits and repetitive behaviors, and the symptom onset during the neonatal period. Research focusing on the effect of gene-by-gene interactions or genetic susceptibility to detrimental environmental challenges may further understanding of the complex etiology for autism.

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Assessing autism-like behavior in mice: Variations in social interactions among inbred strains

Cited by 234 publications

References 53 publications

Automated measurement of mouse social behaviors using depth sensing, video tracking, and machine learning

Automated measurement of mouse social behaviors using depth sensing, video tracking, and machine learning

Sex differences in animal models of psychiatric disorders

Advances in behavioral genetics: mouse models of autism

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