Editors' ChoiceNeuroscience

A prosocial neuroligin

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Science Signaling  18 Aug 2020:
Vol. 13, Issue 645, eabe3352
DOI: 10.1126/scisignal.abe3352

NLGN3 links oxytocin signaling, protein synthesis, and social behavior in a mouse model of autism.

Autism spectrum disorder (ASD) is generally characterized by difficulties with social interaction, communication, sensory processing, and traditional learning. The heterogeneity of the disorder, in terms of both symptoms and gene associations, make it challenging to establish causality and, therefore, difficult to treat. In some individuals with autism, baseline amounts of the prosocial hormone oxytocin are low. Using juvenile mice, Hörnberg et al. found that ASD-associated loss of the synaptic adhesion protein neuroligin 3 (NLGN3) reduced oxytocin signaling in “reward centers” of the brain, thus reducing social interaction. Loss of NLGN3 prevented oxytocin-induced firing and disrupted homeostatic protein translation in midbrain dopaminergic neurons in a manner dependent on MAPK-interacting kinases (MNKs). A brain-penetrant MNK inhibitor improved translation homeostasis and social behavior not only in the NLGN3-deficient mice, but also in a second ASD rodent model (specifically the Fragile X syndrome–associated Fmr1 knockout), suggesting that this therapeutic approach may potentially be applicable in patients beyond those with NLGN3 loss.

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