Assessing behavioural and cognitive domains of autism spectrum disorders in rodents: current status and future perspectives

Abstract

The establishment of robust and replicable behavioural testing paradigms with translational value for psychiatric diseases is a major step forward in developing and testing etiology-directed treatment for these complex disorders. Based on the existing literature, we have generated an inventory of applied rodent behavioural testing paradigms relevant to autism spectrum disorders (ASD). This inventory focused on previously used paradigms that assess behavioural domains that are affected in ASD, such as social interaction, social communication, repetitive behaviours and behavioural inflexibility, cognition as well as anxiety behaviour. A wide range of behavioural testing paradigms for rodents were identified. However, the level of face and construct validity is highly variable. The predictive validity of these paradigms is unknown, as etiology-directed treatments for ASD are currently not on the market. To optimise these studies, future efforts should address aspects of reproducibility and take into account data about the neurodevelopmental underpinnings and trajectory of ASD. In addition, with the increasing knowledge of processes underlying ASD, such as sensory information processes and synaptic plasticity, phenotyping efforts should include multi-level automated analysis of, for example, representative task-related behavioural and electrophysiological read-outs.

Intragenic CNTNAP2 Deletions: A Bridge Too Far

“…Also in cultures of cortical neurons from Cntnap2-null C57BL/6J mice, new dendritic spines were formed at normal rates but failed to stabilize [Gdalyahu et al, 2015]. Thus, cellular functions of CNTNAP2 in C57BL/6J and CD1 mice are congruent, which is in stark contrast to the marked differences regarding behavioral and cognitive features with relevance to ASD found among inbred mouse strains [Kas et al, 2014]. These observations indicate that CNTNAP2 is most likely required for the maturation and maintenance of spiny synapses, but not for earlier stages of postnatal development of pyramidal neurons.…”

Temporal dynamics of social hierarchy formation and maintenance in male mice

“…Traditionally, the study of social behaviour in laboratory mice has been limited to brief dyadic interactions occurring in a context separate from the home-cage environment (Brodkin, 2007;Crawley, 2007;Kas et al, 2014). Although these tests reveal behaviour characteristics of individual mice and the relationship between two individuals at a given point in time, they do not provide information about how relationships develop over time or how relationships are adjusted within a large social network.…”

Connecting the CNTNAP2 Networks with Neurodevelopmental Disorders

“…While Caspr2 null mice exhibit some, but not all features of autism, mice with mutations in Nlgn3 exhibit an almost complete recapitulation of autism [Poot, 2013;Rothwell et al, 2014]. It should be pointed out, however, that the genetic background of the mouse strain studied may influence what kind of phenotypes can be observed [Kas et al, 2014].…”

“…repetitive behaviors, and language problems, including dysarthric language, delayed or absent speech or language acquisition [RodenasCuadrado et al, 2014]. In recent reviews of human and mouse studies, CNTNAP2 has also been related to neurodevelopmental disorders such as autism [Poot et al, 2011;Peñagarikano and Geschwind, 2012;Poot, 2013;Kas et al, 2014]. Although CNTNAP2 is clearly associated with impaired development of language, this gene may also be a node in one or several molecular networks governing neurodevelopment [Cristino et al, 2014].…”