Behavioral phenotyping of mouse models of neurodevelopmental disorders: Relevant social behavior patterns across the life span

Ricceri, Laura; Moles, Anna; Crawley, Jacqueline N.

doi:10.1016/j.bbr.2006.08.024

Cited by 93 publications

(70 citation statements)

References 183 publications

(222 reference statements)

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“…[31][32][33] Wagner and colleagues 34,35 investigated abnormalities in neonatal and juvenile mice relevant to neurodevelopmental disorders using sets of behavioral tasks for sensorimotor abilities, learning and memory, and other functional domains. The researchers utilized a test for juvenile play to reveal reduced social interaction in a genetic model for autism, the Engrailed 2 null mouse.…”

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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Section: Behavioral Phenotyping Of Mouse Modelsmentioning

confidence: 99%

Advances in behavioral genetics: mouse models of autism

2007

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“…High tendencies for social interaction in mice have been utilized by biomedical researchers to model aspects of human social behaviors [16,52,66]. The automated 3-chambered social approach task [44] and the social transmission of food preference (STFP) task [62,63] have been applied as assays for modeling components of autistic-like behaviors in mice [15,16,[39][40][41][42]44].…”

Section: Introductionmentioning

confidence: 99%

Olfactory cues are sufficient to elicit social approach behaviors but not social transmission of food preference in C57BL/6J mice

Ryan

Young

Moy

et al. 2008

Behavioural Brain Research

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Mouse models for the study of autistic-like behaviors are increasingly needed to test hypotheses about the causes of autism, and to evaluate potential treatments. Both the automated 3-chambered social approach test and social transmission of food preference have been proposed as mouse behavioral assays with face validity to diagnostic symptoms of autism, including aberrant reciprocal social interactions and impaired communication. Both assays measure aspects of normal social behavior in the mouse. However, little is known regarding the salient cues present in each assay that elicit normal social approach and communication. To deconstruct the critical components, we focused on delivering discrete social and non-social olfactory and visual cues within the context of each assay. Results indicate that social olfactory cues were sufficient to elicit normal sociability in the 3-chambered social approach test On social transmission of food preference, isolated social olfactory cues were sufficient to induce social investigation, but not sufficient to induce food preference. These findings indicate that olfactory cues are important in mouse social interaction, but that additional sensory cues are necessary in certain situations. The present evidence that both the 3-chambered social approach assay and the social transmission of food preference assay require socially relevant cues to elicit normal behavior supports the use of these two assays to investigate autismrelated behavioral phenotypes in mice.

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“…Although mice do not use language, they do display possible social communication mechanisms. Mice emit auditory signals, including ultrasonic vocalizations, and olfactory social signals, including deposition of pheromones in the environment (23, 39, 84,102,157). Conspecifics appear to interpret and respond to these auditory and olfactory emissions.…”

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confidence: 99%

“…Ideal mouse models will incorporate components relevant to all three diagnostic symptoms, and some of the associated symptoms. Modest goals for paralleling some of the core and associated symptoms of autism are likely to yield mouse models with considerable heuristic value for understanding genetic mechanisms and evaluating potential treatments for autism.To date, several mouse models of autism have been proposed (3,157,207). One approach is targeted gene mutation for neurotransmitters and developmental genes that may regulate social behaviors.…”

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confidence: 99%

“…Mice are a highly social species, displaying social investigation of an unfamiliar conspecific (an individual of the same species), communal nesting, sleeping in group huddles, aggression directed towards intruders, sexual approach and mating behavior patterns, parental care of the pups and juvenile play (16,76,111,146,157,160). Behavioral neuroscientists use standardized scoring methods to quantitate these various types of social interactions in mice (14,18, 25,59,117,123,157,193,194). Starting from this existing literature, we designed an automated apparatus to detect unusually low levels of normal mouse sociability that may be analogous to the deficits in appropriate social interaction seen in many cases of autism (48,124,134,136,138).…”

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Mouse Behavioral Assays Relevant to the Symptoms of Autism*

2007

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While the cause of autism remains unknown, the high concordance between monozygotic twins supports a strong genetic component. The importance of genetic factors in autism encourages the development of mutant mouse models, to advance our understanding of biological mechanisms underlying autistic behaviors. Mouse models of human neuropsychiatric diseases are designed to optimize (i) face validity (resemblance to the human symptoms) (ii) construct validity (similarity to the underlying causes of the disease) and (iii) predictive validity (expected responses to treatments that are effective in the human disease). There is a growing need for mouse behavioral tasks with all three types of validity, to define robust phenotypes in mouse models of autism. Ideal mouse models will incorporate analogies to the three diagnostic symptoms of autism: abnormal social interactions, deficits in communication and high levels of repetitive behaviors. Social approach is tested in an automated three chambered apparatus that offers the subject a choice between spending time with another mouse, with a novel object, or remaining in an empty familiar environment. Reciprocal social interaction is scored from videotapes of interactions between pairs of unfamiliar mice. Communication is evaluated by measuring emission and responses to vocalizations and olfactory cues. Repetitive behaviors are scored for measures of grooming, jumping, or stereotyped sniffing of one location or object. Insistence on sameness is modeled by scoring a change in habit, for example, reversal of the spatial location of a reinforcer in the Morris water maze or T-maze. Associated features of autism, for example, mouse phenotypes relevant to anxiety, seizures, sleep disturbances and sensory hypersensitivity, may be useful to include in a mouse model that meets some of the core diagnostic criteria. Applications of these assays include (i) behavioral phenotyping of transgenic and knockout mice with mutations in genes relevant to autism; (ii) characterization of inbred strains of mice; (iii) evaluation of environmental toxins; (iv) comparison of behavioral phenotypes with genetic factors, such as unusual expression patterns of genes or unusual single nucleotide polymorphisms; and (v) evaluation of proposed therapeutics for the treatment of autism. Pathol 2007;17:448-459. Brain STRATEGIES FOR DESIGNING MOUSE MODELS OF AUTISMDeveloping rodent behavioral tasks relevant to the symptoms of autism presents a unique challenge to behavioral neuroscientists. Rodent models of neuropsychiatric disorders have a long and illustrious history. Models of generalized anxiety disorder have focused on approach-avoidance conflict behaviors, including the elevated plus maze, light↔dark exploration, marble burying and Vogel thirsty-lick conflict tests (19, 35, 41, 44,60,62,88,163,172). Cognitive deficits in Alzheimer's models are detected with learning and memory tests, including (i) spatial navigation tasks such as the Morris water maze, Barnes maze, radial maze and T-maze; (ii) working memor...

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Behavioral phenotyping of mouse models of neurodevelopmental disorders: Relevant social behavior patterns across the life span

Cited by 93 publications

References 183 publications

Advances in behavioral genetics: mouse models of autism

Advances in behavioral genetics: mouse models of autism

Olfactory cues are sufficient to elicit social approach behaviors but not social transmission of food preference in C57BL/6J mice

Mouse Behavioral Assays Relevant to the Symptoms of Autism*

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