Behavioural phenotyping assays for mouse models of autism

Silverman, Jill L.; Yang, Mu; Lord, Catherine; Crawley, Jacqueline N.

doi:10.1038/nrn2851

Cited by 1,289 publications

(1,435 citation statements)

References 173 publications

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“…We will not go into depth discussing behavioural testing of autistic mouse models-a comprehensive review is already available [77]. However, the validity of any behavioural test in mice must always be carefully considered in relation to human symptoms.…”

Section: Making Progress In Mouse Models Of Autismmentioning

confidence: 99%

Shank mutant mice as an animal model of autism

Yoo

Bakes

Bradley

et al. 2014

Phil. Trans. R. Soc. B

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In this review, we focus on the role of the Shank family of proteins in autism. In recent years, autism research has been flourishing. With genetic, molecular, imaging and electrophysiological studies being supported by behavioural studies using animal models, there is real hope that we may soon understand the fundamental pathology of autism. There is also genuine potential to develop a molecular-level pharmacological treatment that may be able to deal with the most severe symptoms of autism, and clinical trials are already underway. The Shank family of proteins has been strongly implicated as a contributing factor in autism in certain individuals and sits at the core of the alleged autistic pathway. Here, we analyse studies that relate Shank to autism and discuss what light this sheds on the possible causes of autism.

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Section: Making Progress In Mouse Models Of Autismmentioning

confidence: 99%

Shank mutant mice as an animal model of autism

Yoo

Bakes

Bradley

et al. 2014

Phil. Trans. R. Soc. B

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“…Adapted from similar behavioral assays that model social anxiety-like states (Bailey and Crawley, 2009;Bruchas et al, 2011;Felix-Ortiz and Tye, 2014;Silverman et al, 2010), the social approach assay measures the time a mouse spends in the presence of a novel conspecific (social zone) (Figure 2a). Less time spent in the social zone indicates a social anxiety-like state that is reversible using traditional anxiolytics, such as diazepam (Stemmelin et al, 2007).…”

Section: Chemogenetic Activation Of Gαs Signaling In the Bla Is Suffimentioning

confidence: 99%

“…Behavior-Social Approach (SA) Social approach behavior was based and modified on previous studies (Silverman et al, 2010). Lighting was measured at~200 lux.…”

Section: Behavior-open Field Test (Oft)mentioning

confidence: 99%

Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

Siuda

Al‐Hasani

McCall

et al. 2016

Neuropsychopharmacol

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Anxiety disorders are debilitating psychiatric illnesses with detrimental effects on human health. These heightened states of arousal are often in the absence of obvious threatening cues and are difficult to treat owing to a lack of understanding of the neural circuitry and cellular machinery mediating these conditions. Activation of noradrenergic circuitry in the basolateral amygdala is thought to have a role in stress, fear, and anxiety, and the specific cell and receptor types responsible is an active area of investigation. Here we take advantage of two novel cellular approaches to dissect the contributions of G-protein signaling in acute and social anxiety-like states. We used a chemogenetic approach utilizing the Gαs DREADD (rM3Ds) receptor and show that selective activation of generic Gαs signaling is sufficient to induce acute and social anxiety-like behavioral states in mice. Second, we use a recently characterized chimeric receptor composed of rhodopsin and the β 2 -adrenergic receptor (Opto-β 2 AR) with in vivo optogenetic techniques to selectively activate Gαs β-adrenergic signaling exclusively within excitatory neurons of the basolateral amygdala. We found that optogenetic induction of β-adrenergic signaling in the basolateral amygdala is sufficient to induce acute and social anxiety-like behavior. These findings support the conclusion that activation of Gαs signaling in the basolateral amygdala has a role in anxiety. These data also suggest that acute and social anxiety-like states may be mediated through signaling pathways identical to β-adrenergic receptors, thus providing support that inhibition of this system may be an effective anxiolytic therapy.

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“…The temperature and humidity in the holding room was controlled at 21±1°C, and 55±5% respectively, and a conventional ad libitum food and water diet was supplied by the LAU. Olfactory testing was conducted only in adulthood (week 16) because juvenile mice are known to respond unpredictably to odors [42]. The fear conditioning test was also only conducted once at the end of behavior tests (week 17), to avoid any residual influence of the aversive nature of that test.…”

Section: Animals and Sample Collectionsmentioning

confidence: 99%

A single low dose of valproic acid in late prenatal life alters postnatal behavior and glutamic acid decarboxylase levels in the mouse

Wei

Lam

et al. 2016

Behavioural Brain Research

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Rationale Rodents exposed to valproic acid (VPA) in prenatal life exhibit post-natal characteristics analogous to autism spectrum disorder (ASD). Many previous studies used relatively high doses of VPA during early pregnancy, potentially confounding interpretation because the offspring are the "survivors" of a toxic insult. Low dose or late gestation exposure has not been widely studied. Objectives We examined the behavioral sequelae of late gestation exposure to low dose VPA in the mouse. We also examined postnatal levels of glutamic acid decarboxylase (GAD65 and GAD67) as markers for GABA neurons, because GABA pathology and subsequent excitatory/inhibitory imbalance is strongly implicated in ASD. Methods Pregnant C57BL/6N mice received a single subcutaneous injection of 100 or 200 mg/kg on gestation day 17. The control group received a saline injection on the same day. The offspring were tested in a battery of behavioral tests in adolescence and adulthood. Six brain regions were harvested and GAD65 and GAD67 were measured by western blotting. Results Compared to saline-exposed controls, adult mice exposed to prenatal VPA had impaired novel object exploration and fear conditioning anomalies. GAD67 was decreased in midbrain, olfactory bulb, prefrontal cortex and increased in cerebellum, hippocampus and striatum; GAD65 was decreased in all 6 regions. ConclusionsOur results suggest that a low dose of VPA in late pregnancy has persistent effects on brain development, and in particular the GABA system, which 3 may be relevant to ASD. Further attention to the impact of gestation time and dose of exposure in VPA-induced ASD models is encouraged.

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Behavioural phenotyping assays for mouse models of autism

Cited by 1,289 publications

References 173 publications

Shank mutant mice as an animal model of autism

Shank mutant mice as an animal model of autism

Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

A single low dose of valproic acid in late prenatal life alters postnatal behavior and glutamic acid decarboxylase levels in the mouse

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