Autism spectrum disorders (ASD) are heterogeneous neurodevelopmental disorders characterized by deficits in social interaction and social communication, restricted interests and repetitive behaviors. Abnormalities in language development, mental retardation and epilepsy are often observed in autistic children and, conversely, several forms of epilepsy also display ASD. Given the high comorbidity between ASD and epilepsy, the possibility of a common genetic basis for both diseases has been proposed. Synapsins (Syns) are a family of synaptic vesicle phosphoproteins encoded by the SynI, SynII and SynIII genes. The Syn gene family is a good candidate for the synaptic epilepsy/ASD pathway, as Syns regulate synaptic transmission and plasticity with distinct roles in excitatory and inhibitory neurons. Moreover, genetic mapping analysis identified variations in the SynII gene as significantly contributing to epilepsy predisposition and a few SynII variants potentially associated with epilepsy and ASD. Mice lacking SynII mice experience epileptic seizures starting at 2-3 months of age and display an array of mild cognitive impairments, including emotional and spatial memory deficits. However, the effects of the SynIIisoform on the various aspects of social behavior have never been studied.
Aim of our study was to analyze whether deletion of SynIIgene in mice causes social communication deficits at adulthood.
Social and vocal repertoires of three month-old Syn II males (n= 11 Syn II+/+, n= 22 Syn II+/-, n= 10 Syn II-/- ) were assessed during the male-female interaction test. The 3-min test session was conducted in a clean cage with clean bedding, representing a novel situation for both the male subject and the female partner. Social behaviors and ultrasonic vocalizations were recorded and subsequently analyzed by Observer X (Noldus) and Avisoft SasLab Pro (Avisoft Bioacoustics).
Analysis of social and vocal repertoires revealed a clear social investigation deficit (both in frequency: F(2,40)=3,145, P<0.05 and duration : F(2,40)=6,343, P<0.005) in Syn II-/- male mice associated with an absence of emission of ultrasonic vocalizations (F(2,40)=3,145, P<0.001) in this social context. Olfactory investigation allows the mouse to gather biologically meaningful information on the identity of a conspecific, such as social status and sex. There is compelling evidence that ultrasonic vocalizations in this context not only serve to establish or to maintain social contact but are predictors of mating opportunities and are associated with reward expectations. Specifically, Syn II -/- males showed a significant reduction in nose-to-nose, body and anogenital sniffing toward a sexually receptive female, all behaviors classically performed by mice in this social context. No significant effect of genotype was found on behavioral measurements commonly used to evaluate general exploratory activity
The social communication deficit observed in Syn II-/- mice supports the view that this gene is also involved in the expression of social behavioral traits associated with ASD and suggests as this mutant mouse line represents a good experimental model to study ASD with epilepsy.