Social Isolation Alters Social and Mating Behavior in the R451C Neuroligin Mouse Model of Autism

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder typified by impaired social communication and restrictive and repetitive behaviors. Mice serve as an ideal candidate organism for studying the neural mechanisms that subserve these symptoms. The Neuroligin-3 (NL3) mouse, expressing a R451C mutation discovered in two Swedish brothers with ASD, exhibits impaired social interactions and heightened aggressive behavior towards male mice. Social interactions with female mice have not been characterized and in the present study were assessed in male NL3R451C and WT mice. Mice were housed in social and isolation conditions to test for isolation-induced increases in social interaction. Tests were repeated to investigate potential differences in interaction in naïve and experienced mice. We identified heightened interest in mating and atypical aggressive behavior in NL3R451C mice. NL3R451C mice exhibited normal social interaction with WT females, indicating that abnormal aggressive behavior towards females is not due to altered motivation to engage. Social isolation rearing heightened interest in social behavior in all mice. Isolation housing selectively modulated the response to female pheromones in NL3R451C mice. This study is the first to show altered mating behavior in the NL3R451C mouse and has provided new insights into the aggressive phenotype in this model.

Characterization of a gene-trap knockout mouse model ofScn2aencoding voltage-gated sodium channel Nav1.2

“…Thus socio-sexual olfactory investigatory preference was used to further understand why the Scn2a gtKO/gtKO mice display no mating behavior. Scn2a gtKO/gtKO males show a preference for the male scent instead of the estrus female scent, which was also reported in a Neuroligin-3 mouse model of neurodevelopmental disorders [50]. Future studies are needed to determine the role of Scn2a on hormone regulation which is suggested to play a role in neurodevelopment [51,52].…”

Encounters between pairs of unfamiliar dogs in a dog park

“…A trend for a more frequent display of moving away from the other dog was observed for singly kept dogs. Various studies report effects of early social isolation on human and animal social skills and behavior (Burrows et al, 2017; Dog encounters Harlow et al, 1965;Lykken, 1994;Wongwitdecha & Marsden, 1996). In pet dogs, we can expect that social competence with regard to conspecifics can be selectively affected by limited exposure to other dogs.…”

Mice with an autism‐associated R451C mutation in neuroligin‐3 show a cautious but accurate response style in touchscreen attention tasks

“…[11][12][13][14][15] Although this specific mutation is rare in clinical populations, a clustering of ASD associated mutations found in neurexins, neuroligins and their downstream binding partner Shank3 9,[16][17][18] add to the hypothesis that disruption of this pathway contributes to the disorder. Our group, and others, have discovered impairments in NL3 R451C mice in core behavioural traits, including social impairment, presence of restrictive and repetitive behaviours and aggression; [11][12][13][19][20][21][22][23][24] however, the role of this mutation in attentional processing has not been previously investigated.…”