Behavioural assessment of a neurexin knockout mouse model

Abstract

Synapse organisers are crucial players in synapse development and maintenance. Neurexins are the master regulators of synapse formation. They are presynaptic proteins that connect the two neurons and facilitate signal transmission. Deletion or mutations causing altered neurexin expression has been implicated in autism spectrum disorder (ASD), schizophrenia (SCZ), epilepsy, and other neurological or psychiatric disorders. In this study, I investigated a relatively understudied but well-expressed isoform of neurexin. Since neurexins are linked with ASD and SCZ, I performed a comprehensive behavioural study on a mouse model lacking the specific isoform of neurexin and littermate wildtype (WT) mice. The behavioural tests included open field test (OFT), buried food test, visual cliff test, elevated plus maze (EPM), Crawley's three-chamber test, novel object recognition (NOR), Barnes maze (BM), and contextual fear conditioning (CFC). Mice lacking the specific isoform of neurexin displayed deficits in social memory, social novelty preference, and spatial memory compared to WT mice, which are core symptoms of ASD and SCZ, but had normal object recognition memory and fear memory. In addition, both genotypes displayed normal locomotor activity, anxiety-related behaviours, visual perception, and olfaction. Thus, the results indicate that specific neurexin isoforms may contribute to regulating social behaviour and spatial memory.