Environmental enrichment modulates affiliative and aggressive social behaviour in the neuroligin-3 R451C mouse model of autism spectrum disorder

E L Burrows; L Koyama; C May; E L Hill-Yardin; A J Hannan

doi:10.1016/j.pbb.2020.172955

Environmental enrichment modulates affiliative and aggressive social behaviour in the neuroligin-3 R451C mouse model of autism spectrum disorder

Pharmacol Biochem Behav. 2020 Aug:195:172955. doi: 10.1016/j.pbb.2020.172955. Epub 2020 May 29.

Authors

E L Burrows¹, L Koyama², C May², E L Hill-Yardin³, A J Hannan⁴

Affiliations

¹ Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia. Electronic address: Burrowse@unimelb.edu.au.
² Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia.
³ School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia.
⁴ Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Parkville, VIC, Australia.

PMID: 32474162
DOI: 10.1016/j.pbb.2020.172955

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by impairments in social communication and the presence of restrictive and repetitive behaviours. A mouse model expressing an autism-associated R451C mutation in the gene encoding the synaptic adhesion protein neuroligin-3 (NL3) has been extensively characterised and shows altered behaviour relevant to core traits observed in ASD. Reported impairments in social behaviours in NL3^R451C mice however remain controversial due to inconsistent findings in various assays across different laboratories. Such inconsistencies could plausibly be explained by an increased susceptibility of the NL3^R451C mouse social phenotype to environmental modulation. To address this, NL3^R451C mice were housed in standard or enriched housing from 4 weeks of age prior to behavioural testing. Enrichment rearing enhanced direct interactions with the stranger mouse in all mice in the three-chamber social interaction test however, NL3^R451C mice did not show impairment in social interaction in the three-chamber test, in contrast with previous reports. Environmental enrichment enhanced aggressive behaviour in all mice, and did not specifically alter the heightened aggressive phenotype previously described in NL3^R451C mice. Specific genotype effects of enrichment included reduced anxiety-like behaviour in WT mice, and lower locomotor activity levels in NL3 mice. While genotype-specific effects of enrichment were not seen on social behaviour, the general increase in affiliative social interaction and aggression seen in all mice, indicates that these behaviours, are vulnerable to change based on housing condition. Mouse models expressing ASD-associated mutations have great utility in elucidating the neurobiology underling development of core traits and it is crucial that efforts are focussed on those models exhibiting robust phenotypes. In light of the findings in the present study, we suggest approaches to improve replicability and reproducibility in mouse models of ASD.

Keywords: Aggression; Autism spectrum disorder; Environmental enrichment; Neuroligin-3; R451C; Social interaction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aggression / psychology*
Animals
Anxiety
Autism Spectrum Disorder / psychology*
Behavior, Animal
Body Weight
Cell Adhesion Molecules, Neuronal / genetics*
Disease Models, Animal
Female
Housing, Animal*
Locomotion
Male
Maze Learning
Membrane Proteins / genetics*
Mice
Mice, Inbred C57BL
Mutation*
Nerve Tissue Proteins / genetics*
Physical Conditioning, Animal / psychology*
Social Interaction*

Substances

Cell Adhesion Molecules, Neuronal
Membrane Proteins
Nerve Tissue Proteins
neuroligin 3