Novel behavioural phenotypes in the Neuroligin-3 genetic mouse model of Autism Spectrum Disorder

Cellular & Systems Neuroscience Seminars

Rodent models are used to investigate mechanisms underlying behavioural traits in complex diseases such as Autism Spectrum Disorder (ASD). To address the shortcomings of traditional rodent behavioural testing, we are using touchscreens to test multiple cognitive domains in mice, analogous to those used in clinic assessments. Furthermore, we are investigating ultrasonic social calls as a proxy for communication impairments using a novel sound recognition algorithm that was originally developed to detect changes in affective prosody in humans with ASD. We are applying these novel methods to expand the behavioural characterisation of mice expressing the ASD-associated R451C mutation in the synaptic adhesion gene neuroligin-3 (NL3). Using touchscreens we have identified impaired behavioural flexibility and subtle changes in attentional processing in the NL3 mouse. Our novel sound recognition algorithm is able to accurately characterise mouse calls automatically and objectively, and has uncovered impairments in vocalisation in NL3 mice. Together, these approaches have identified novel behavioural phenotypes, analogous to human ASD behaviours.