Hippocampal Neuroligin-2 Overexpression Leads to Reduced Aggression and Inhibited Novelty Reactivity in Rats

Abstract

Disturbances of the excitation/inhibition (E/I) balance in the brain were recently suggested as potential factors underlying disorders like autism and schizophrenia resulting in associated behavioral alterations including changes in social and emotional behavior as well as abnormal aggression. Neuronal cell adhesion molecules (nCAMs) and mutations in these genes were found to be strongly implicated in the pathophysiology of these disorders. Neuroligin2 (nlgn2) is a postsynaptic cell adhesion molecule, which is predominantly expressed at inhibitory synapses and required for synapse specification and stabilization. Changes in the expression of nlgn2 were shown to result in alterations of social behavior as well as altered inhibitory synaptic transmission, hence modifying the E/I balance. In our study, we focused on the role of nlgn2 in the dorsal hippocampus in the regulation of emotional and social behaviors. To this purpose, we injected an AAV construct overexpressing nlgn2 in the hippocampus of rats and investigated the effects on behavior and on markers for the E/I ratio. We could show an increase in GAD65, a GABA-synthesizing protein in neuronal terminals, and furthermore, reduced exploration of novel stimuli and less offensive behavior. Our data suggest nlgn2 in the hippocampus to be strongly implicated in maintaining the E/I balance in the brain and thereby modulating social and emotional behavior.

Stress and the social brain: behavioural effects and neurobiological mechanisms

“…Chronic stress reduces NLGN-2, but not NLGN-1, expression throughout the hippocampus in parallel with decreased sociability and increased aggression in rats 13 [ figure, part c]. Hippocampal overexpression of NLGN-2 reduced aggressive behavior in rats 208 .…”

Social deficits induced by peripubertal stress in rats are reversed by resveratrol

“…The samples for western blot were prepared as previously described (Kohl et al, 2013). Eight micrograms of protein was loaded and resolved on a 10% polyacrylamide gel and transferred onto a nitrocellulose membrane (Whatman Protran, Dassel, Germany).…”

Genetic and non-genetic determinants of aggression in combat sports

“…The hippocampus may be involved in aggression-related behavior. Considering the findings of Kohl et al [72], it must be stated that individuals with an overexpression of NLGN2 in the hippocampus show increased inhibition in novelty-induced exploration and reduced aggressive behavior.…”

“…Kohl et al [72] studied changes in the behavior of rats following the injection of a vector with NLGN2 to the hippocampus. The vector was prepared in such a way to ensure overexpression of the NLGN2 gene.…”

“…In the case of keeping down -a strong parameter for offensive behavior -they observed that NLGN2-OE animals spent less time keeping down the intruder compared to controls with the empty virus. Kohl et al [72] increased the overexpression of NLGN2, particularly in the dorsal hippocampus of rats, by using an adeno-associated virus, and observed behavioral changes in terms of reduced novelty-induced exploration and decreased offensive behaviour. The hippocampus may be involved in aggression-related behavior.…”