Format

Send to

Choose Destination
Front Cell Neurosci. 2018 Aug 3;12:234. doi: 10.3389/fncel.2018.00234. eCollection 2018.

Altered Amygdala Excitation and CB1 Receptor Modulation of Aggressive Behavior in the Neuroligin-3R451C Mouse Model of Autism.

Author information

1
School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia.
2
Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
3
Department of Pharmacology, University of Auckland, Auckland, New Zealand.
4
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia.
5
Department of Anatomy and Neuroscience, University of Melbourne, Parkville, VIC, Australia.
6
Department of Physiology, University of Melbourne, Parkville, VIC, Australia.

Abstract

Understanding neuronal mechanisms underlying aggression in patients with autism spectrum disorder (ASD) could lead to better treatments and prognosis. The Neuroligin-3 (NL3)R451C mouse model of ASD has a heightened aggressive phenotype, however the biological mechanisms underlying this behavior are unknown. It is well established that NL3R451C mice have imbalanced excitatory and inhibitory synaptic activity in the hippocampus and somatosensory cortex. The amygdala plays a role in modulating aggressive behavior, however potential changes in synaptic activity in this region have not previously been assessed in this model. We investigated whether aggressive behavior is robustly present in mice expressing the R451C mutation, following back-crossing onto a congenic background strain. Endocannabinoids influence social interaction and aggressive behavior, therefore we also studied the effects of cannabinoid receptor 1 (CB1) agonist on NL3R451C mice. We report that NL3R451C mice have increased amplitude of miniature excitatory postsynaptic currents (EPSCs) with a concomitant decrease in the amplitude of inhibitory postsynaptic currents (IPSCs) in the basolateral amygdala. Importantly, we demonstrated that NL3R451C mice bred on a C57Bl/6 background strain exhibit an aggressive phenotype. Following non-sedating doses (0.3 and 1.0 mg/kg) of the CB1 receptor agonist WIN55,212-2 (WIN), we observed a significant reduction in aggressive behavior in NL3R451C mice. These findings demonstrate altered synaptic activity in the basolateral amygdala and suggest that the NL3R451C mouse model is a useful preclinical tool to understand the role of CB1 receptor function in aggressive behavior.

KEYWORDS:

WIN-55212-2; aggression; autism spectrum disorder; cannabinoid receptor; neuroligin; synaptic currents

Supplemental Content

Full text links

Icon for Frontiers Media SA Icon for PubMed Central
Loading ...
Support Center