Autism‐like behavioral phenotypes in BTBR T+tf/J mice

McFarlane, Hewlet G.; Kusek, G. K.; Yang, Mu; Phoenix, Jennifer L.; Bolivar, Valerie J.; Crawley, Jacqueline N.

doi:10.1111/j.1601-183x.2007.00330.x

Cited by 715 publications

(866 citation statements)

References 83 publications

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“…To demonstrate the applicability of this vision-based approach to largescale phenotypic analysis, we characterized the home-cage behaviour of four strains of mice, including the wild-derived strain CAST / EiJ, the BTBR strain, a potential model of autism 4 , as well as two of the most popular inbred mouse strains C57BL / 6J and DBA / 2J. We video recorded n = 7 mice of each strain during one 24-h session, encompassing a complete light -dark cycle.…”

Section: Resultsmentioning

confidence: 99%

“…Although automation in and of itself is not a panacea for neurobehavioural experiments 2 , it allows for addressing an entirely new set of questions about mouse behaviour and to conduct experiments on time scales that are orders of magnitude larger than those traditionally assayed. For example, reported tests of grooming behaviour span time scales of minutes 3,4 , whereas an automated analysis will allow for analysis of this behaviour over hours or even days and weeks.…”

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confidence: 99%

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Automated home-cage behavioural phenotyping of mice

et al. 2010

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Neurobehavioural analysis of mouse phenotypes requires the monitoring of mouse behaviour over long periods of time. In this study, we describe a trainable computer vision system enabling the automated analysis of complex mouse behaviours. We provide software and an extensive manually annotated video database used for training and testing the system. Our system performs on par with human scoring, as measured from ground-truth manual annotations of thousands of clips of freely behaving mice. As a validation of the system, we characterized the home-cage behaviours of two standard inbred and two non-standard mouse strains. From these data, we were able to predict in a blind test the strain identity of individual animals with high accuracy. Our video-based software will complement existing sensor-based automated approaches and enable an adaptable, comprehensive, high-throughput, fi ne-grained, automated analysis of mouse behaviour. A utomated quantitative analysis of mouse behaviour will have a signifi cant role in comprehensive phenotypic analyses -both on the small scale of detailed characterization of individual gene mutants and on the large scale of assigning gene function across the entire mouse genome 1 . One key benefi t of automating behavioural analysis arises from inherent limitations of human assessment, namely, cost, time and reproducibility. Although automation in and of itself is not a panacea for neurobehavioural experiments 2 , it allows for addressing an entirely new set of questions about mouse behaviour and to conduct experiments on time scales that are orders of magnitude larger than those traditionally assayed. For example, reported tests of grooming behaviour span time scales of minutes 3,4 , whereas an automated analysis will allow for analysis of this behaviour over hours or even days and weeks.Indeed, the signifi cance of alterations in home-cage behaviour has recently gained attention as an eff ective means of detecting perturbations in neural circuit function -both in the context of disease detection and more generally to measure food consumption and activity parameters 5 -10 . Previous automated systems (see refs 8, 9, 11, 12 and Supplementary Note ) rely mostly on the use of simple detectors such as infrared beams to monitor behaviour. Th ese sensor-based approaches tend to be limited in the complexity of the behaviour that they can measure, even in the case of costly commercial systems using transponder technologies 13 . Although such systems can be used eff ectively to monitor locomotor activity and perform operant conditioning, they cannot be used to study homecage behaviours such as grooming, hanging, jumping and smaller movements (termed ' micromovements ' below). Visual analysis is a potentially powerful complement to these sensor-based approaches for the recognition of such fi ne animal behaviours.Advances in computer vision and machine learning over the last decade have yielded robust computer vision systems for the recognition of objects 14,15 and human actions (see Moeslund et ...

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Automated home-cage behavioural phenotyping of mice

et al. 2010

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“…2) mice (Japan SLC, Inc.) were used for in vivo imaging (see Supplementary Tables 1-7 for the number and ages of animals in each experiment). The following ASD mouse models were used in this study: patDp/ þ mice with paternal duplication of chromosome 7c 24 , NLG R451C mice with a point mutation corresponding to the human NLGN-3 R451C 15 and BTBR T þ tf mice 43 . Constructs of PSD-95-GFP were previously described 34,61 .…”

Section: Methodsmentioning

confidence: 99%

“…We further extended in vivo imaging analyses of PSD-95-GFP-( þ ) spines to the third ASD mouse model, BTBR mice 43 . Dynamics of PSD-95-GFP-( þ ) spines in the AFC of BTBR mice at postnatal week 3 was once more upregulated to a similar extent (Supplementary Fig.…”

Section: Nature Communications | Doi: 101038/ncomms5742mentioning

confidence: 99%

Enhanced synapse remodelling as a common phenotype in mouse models of autism

et al. 2014

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Developmental deficits in neuronal connectivity are considered to be present in patients with autism spectrum disorders (ASDs). Here we examine this possibility by using in vivo spine imaging in the early postnatal cortex of ASD mouse models. Spines are classified by the presence of either the excitatory postsynaptic marker PSD-95 or the inhibitory postsynaptic marker gephyrin. ASD mouse models show consistent upregulation in the dynamics of PSD-95-positive spines, which may subsequently contribute to stable synaptic connectivity. In contrast, spines receiving inputs from the thalamus, detected by the presence of gephyrin clusters, are larger, highly stable and unaffected in ASD mouse models. Importantly, two distinct mouse models, human 15q11-13 duplication and neuroligin-3 R451C point mutation, show highly similar phenotypes in spine dynamics. This selective impairment in dynamics of PSD-95-positive spines receiving intracortical projections may be a core component of early pathological changes and be a potential target of early intervention.

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“…For this, we chose BTBR T + tf/J mice, which present with a spectrum of behavioral perturbations (e.g., impaired sociability and repetitive behavior), as well as neuropathological abnormalities (e.g., absence of corpus callosum, i.e., deficient long-range connectivity) consistent with autism [19,20], and are commonly used in autism research. We report that ECT transiently reverses autism-like behavioral abnormalities in BTBR mice, and that therapeutic effects of ECT may be partly regulated by central oxytocin signaling.…”

Section: Introductionmentioning

confidence: 99%

Autism-Like Behavior in BTBR Mice Is Improved by Electroconvulsive Therapy

et al. 2015

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Autism is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. Incidence of autism is higher than earlier estimates, and treatments have limited efficacy and are costly. Limited clinical and experimental evidence suggest that patients with autism may benefit from electroconvulsive therapy (ECT). We examined the therapeutic potential of ECT in BTBR T+ tf/j mice, which represent a validated model of autism. A series of 13 electroconvulsive shocks (ECS) delivered twice a day over 7 days reversed core autism-like behavioral abnormalities-impaired sociability, social novelty, and repetitive behavior-when the animals were tested 24 h after the last ECS. The effect lasted up to 2 weeks after ECT. Neither single ECS nor a series of 6 ECS modified animals' behavior. Chronic infusion into the lateral brain ventricle of a preferential oxytocin receptor blocker (2S)-2-Amino--(methylsulfonyl)butanamide hydrochloride abolished ECTinduced improvement of sociability and mitigated improvement of social novelty but did not affect ECT-induced reversal of repetitive behavior. These proof-of-principle experiments suggest that ECT may, indeed, be useful in the treatment of autism, and that its therapeutic effects may be mediated, in part, by central oxytocin signaling.

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Autism‐like behavioral phenotypes in BTBR T+tf/J mice

Cited by 715 publications

References 83 publications

Automated home-cage behavioural phenotyping of mice

Automated home-cage behavioural phenotyping of mice

Enhanced synapse remodelling as a common phenotype in mouse models of autism

Autism-Like Behavior in BTBR Mice Is Improved by Electroconvulsive Therapy

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