Behavioral Phenotyping for Autism Spectrum Disorders in Mice

Chang, Yu‐Chi; Cole, Toby B.; Costa, Lucio G.

doi:10.1002/cptx.19

Cited by 75 publications

(71 citation statements)

References 68 publications

(152 reference statements)

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“…We tested mice for 5 min with a 5 min baseline in an open-field apparatus (43 cm × 43 cm × 33 cm) while videotaping, and investigators blinded to experimental conditions scored eight different commonly observed behaviors including anogenital sniffing (ag), nose-to-nose (n2n), anogenital sniffing while following the stimulus mouse (ag/follow), following (follow), orienting to the stimulus mouse (orient), approaching the stimulus mouse (approach), investigation of the stimulus mouse (investigation), and being investigated by the stimulus mouse (investigated by stim), adapted from refs. 42,43 . Rare behaviors, such as being chased or chasing, grooming, or side-by-side huddling were also scored but then were excluded due to very low frequencies.…”

Section: Methodsmentioning

confidence: 99%

Prefrontal parvalbumin interneurons require juvenile social experience to establish adult social behavior

et al. 2020

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Social isolation during the juvenile critical window is detrimental to proper functioning of the prefrontal cortex (PFC) and establishment of appropriate adult social behaviors. However, the specific circuits that undergo social experience-dependent maturation to regulate social behavior are poorly understood. We identify a specific activation pattern of parvalbuminpositive interneurons (PVIs) in dorsal-medial PFC (dmPFC) prior to an active bout, or a bout initiated by the focal mouse, but not during a passive bout when mice are explored by a stimulus mouse. Optogenetic and chemogenetic manipulation reveals that brief dmPFC-PVI activation triggers an active social approach to promote sociability. Juvenile social isolation decouples dmPFC-PVI activation from subsequent active social approach by freezing the functional maturation process of dmPFC-PVIs during the juvenile-to-adult transition. Chemogenetic activation of dmPFC-PVI activity in the adult animal mitigates juvenile isolationinduced social deficits. Therefore, social experience-dependent maturation of dmPFC-PVI is linked to long-term impacts on social behavior.

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Section: Methodsmentioning

confidence: 99%

Prefrontal parvalbumin interneurons require juvenile social experience to establish adult social behavior

et al. 2020

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“…Changes in repetitive behavior and anxiety levels were evaluated through the marble burying test in line with previously described methods . The trials were recorded using a Sony Cyber‐shot DSC‐W800 20.1 MP camera.…”

Section: Methodsmentioning

confidence: 99%

“…The three‐chamber test was used to measure sociability as previously described . The sociability apparatus (60 cm L × 45 cm W × 26 cm H) was made from clear acrylic walls and divided into three chambers equal in area.…”

Section: Methodsmentioning

confidence: 99%

“…Changes in repetitive behavior and anxiety levels were evaluated through the marble burying test in line with previously described methods. [60][61][62][63][64] The trials were recorded using a Sony Cyber-shot DSC-W800 20.1 MP camera. The apparatus was a clean standard polycarbonate mouse cage (28.5 cm L × 17.5 cm W × 12 cm H) filled with bedding measuring a height of 3.5 cm.…”

Section: Marble Burying Testmentioning

confidence: 99%

“…The three-chamber test was used to measure sociability as previously described. 61,63,64,67,68 The sociability apparatus (60 cm L × 45 cm W × 26 cm H) was made from clear acrylic walls and divided into three chambers equal in area. The two dividing walls had openings (10 × 10 cm) with removable doors that restricted or permitted access into the adjacent chambers.…”

Section: Three-chamber Sociability Testmentioning

confidence: 99%

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Autism‐related behaviors in the cyclooxygenase‐2‐deficient mouse model

Wong

Bestard-Lorigados

Crawford

2018

Genes Brain and Behavior

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Prostaglandin E2 (PGE2) is an endogenous lipid molecule involved in normal brain development. Cyclooxygenase-2 (COX2) is the main regulator of PGE2 synthesis. Emerging clinical and molecular research provides compelling evidence that abnormal COX2/PGE2 signaling is associated with autism spectrum disorder (ASD). We previously found that COX2 knockout mice had dysregulated expression of many ASD genes belonging to important biological pathways for neurodevelopment. The present study is the first to show the connection between irregular COX2/PGE2 signaling and autism-related behaviors in male and female COX2-deficient knockin, (COX)-2 , mice at young (4-6 weeks) or adult (8-11 weeks) ages. Autism-related behaviors were prominent in male (COX)-2 mice for most behavioral tests. In the open field test, (COX)-2 mice traveled more than controls and adult male (COX)-2 mice spent less time in the center indicating elevated hyperactive and anxiety-linked behaviors. (COX)-2 mice also buried more marbles, with males burying more than females, suggesting increased anxiety and repetitive behaviors. Young male (COX)-2 mice fell more frequently in the inverted screen test revealing motor deficits. The three-chamber sociability test found that adult female (COX)-2 mice spent less time in the novel mouse chamber indicative of social abnormalities. In addition, male (COX)-2 mice showed altered expression of several autism-linked genes: Wnt2, Glo1, Grm5 and Mmp9. Overall, our findings offer new insight into the involvement of disrupted COX2/PGE2 signaling in ASD pathology with age-related differences and greater impact on males. We propose that (COX)-2 mice might serve as a novel model system to study specific types of autism.

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Autism: Animal Models

Bauman¹,

Crawley²,

Berman³

2019

Encyclopedia of Life Sciences

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Autism is a neurodevelopmental disorder characterised by deficits in social interaction, social communication, sensory abnormalities, stereotyped and repetitive behaviours, and restricted interests. Autism spectrum disorder (ASD) has proven difficult to study because of the diversity of its behavioural symptoms, complex genetics and lack of ubiquitous biomarkers. Progress in the development of heuristic animal models has allowed investigators to model some of the core symptoms of autism, including deficits in social interactions, aspects of social communication and stereotyped, repetitive behaviours. Specific hypotheses can now be formulated and tested in mouse, rat and non‐human primate models. Translational applications of animal models have advanced the discovery of therapeutic interventions for treating the core features of ASD. This article describes some of the major behavioural approaches and animal models designed to study neurodevelopmental disorders, with a focus on ASDs. Key Concepts Autism is a complex disorder whose underlying biology is being studied using rodent and non‐human primate animal models. Rodents and non‐human primates are social animals with rich and complex behavioural repertories that make them useful for modelling neurodevelopmental disorders. Many of the behaviours that reflect core deficits in autism, including social communication, social interaction, motor stereotypies and repetitive behaviours, can be modelled in rodents and non‐human primates. Inbred strains of mice can be used to discover genes important for the expression of complex behaviours and can provide insights into the neurobiology of social interactions and social communication. Mice and rats with targeted mutations in risk genes and deletions identified in people with autism provide research tools for investigating mechanistic substrates of the disorder and for discovering therapeutic interventions. Animal models of neurodevelopmental disorders, while important and useful, typically only model specific aspects of a disorder rather that recapitulating its full symptomatology.

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Behavioral Phenotyping for Autism Spectrum Disorders in Mice

Cited by 75 publications

References 68 publications

Prefrontal parvalbumin interneurons require juvenile social experience to establish adult social behavior

Prefrontal parvalbumin interneurons require juvenile social experience to establish adult social behavior

Autism‐related behaviors in the cyclooxygenase‐2‐deficient mouse model

Autism: Animal Models

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