Automated Three‐Chambered Social Approach Task for Mice

Abstract

Autism is diagnosed by three major symptom categories: unusual reciprocal social interactions, impaired communication, and repetitive behaviors with restricted interests. Direct social approach in mice has strong face validity to simple social approach behaviors in humans, which are frequently impaired in autism. This unit presents a basic protocol for a standardized, high-throughput social approach test for assaying mouse sociability. Our automated three-chambered social approach task quantifies direct social approach behaviors when a subject mouse is presented with the choice of spending time with either a novel mouse or a novel object. Sociability is defined as the subject mouse spending more time in the chamber containing the novel target mouse than in the chamber containing the inanimate novel object. The Basic Protocol describes procedures for testing one subject at a time in a single apparatus. A Support Protocol addresses data collection.

The Chromatin-binding Protein HMGN1 Regulates the Expression of Methyl CpG-binding Protein 2 (MECP2) and Affects the Behavior of Mice

“…In the first stage the WT and the Hmgn1 Ϫ/Ϫ mice spent more time in the chamber containing Stranger 1 compared with the time they spent in the chamber containing the empty cup, as expected (41). The HMGN1_OE mice, however, did not display any preference for the unfamiliar mouse, showing an equal interest in Stranger 1 and in the empty cup (Fig.…”

Modeling fragile X syndrome in the <i>Fmr1</i> knockout mouse

“…In the three-chambered sociability task, a subject mouse is evaluated for its exploration of a novel social stimulus (e.g., novel mouse) versus a novel object stimulus (146). Wildtype mice will preferentially explore a novel mouse when given the choice between a novel mouse and a novel object with no social valence.…”

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

“…Social behavior assays have been conducted with many of the mouse models in which imaging studies were conducted. Employing our 3-chambered social approach task, a simple yes-or-no assay for sociability [13], absence of sociability was reported in mice with mutations in genes including Shank3 [15,16], Cntnap2 [17], Pten [18], Tsc1 [19], En2 [20], Gabrb3 [21], Ube3a triplication [22], and oxytocin receptor knockouts [23]. Normal 3-chambered social approach appeared in mice with mutations in genes including oxytocin [24], Shank1 [25], Nlgn2 [26], Ephrin-A [27] and 16p11.2 deletion [28] Variable findings on social approach across laboratories and in mouse lines generated on different genetic backgrounds have been reported for mutations including Fmr1 [29,30], Nlgn3 [31][32][33][34], and Nlgn4 [35,36].…”

“…The initial fundamental question was how to assay autism-relevant behaviors in mice and rats. Our group (JNC) took on this challenge, beginning in 2000, by developing a set of mouse social behavior assays relevant to social approach and appropriate reciprocal interactions, olfactory and ultrasonic vocalization analyses of potential relevance to social communication, and quantitative measures of spontaneous motor stereotypies and repetitive behaviors, along with assessments of mouse behavioral domains relevant to some of the associated symptoms of autism, including intellectual disabilities, anxiety, sensory reactivity, and hyperactivity [6,[8][9][10][11][12][13][14]. These behavioral tests, with high face validity to the diagnostic and associated symptoms of autism, have been widely applied by our laboratory and others to investigate a broad range of g e n e t i c m o u s e m o d e l s o f a u t i s m a n d r e l a t e d neurodevelopmental disorders, as described below and in Table 1.…”