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

Overview

Journal Front Cell Neurosci

Specialty Cell Biology

Date 2018 Aug 21

PMID 30123111

Citations 25

Authors

Suzanne Hosie

Daniel T Malone

Stephanie Liu

Michelle Glass

Paul Anthony Adlard

Anthony John Hannan

Elisa L Hill-Yardin

Affiliations

Soon will be listed here.

Abstract

Understanding neuronal mechanisms underlying aggression in patients with autism spectrum disorder (ASD) could lead to better treatments and prognosis. The Neuroligin-3 (NL3) mouse model of ASD has a heightened aggressive phenotype, however the biological mechanisms underlying this behavior are unknown. It is well established that NL3 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 NL3 mice. We report that NL3 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 NL3 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 NL3 mice. These findings demonstrate altered synaptic activity in the basolateral amygdala and suggest that the NL3 mouse model is a useful preclinical tool to understand the role of CB1 receptor function in aggressive behavior.

Citing Articles

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