Mice with an autism-associated R451C mutation in neuroligin-3 show intact attention orienting but atypical responses to methylphenidate and atomoxetine in the mouse-Posner task

Rationale Atypical attention orienting has been associated with some autistic symptoms, but the neural mechanisms remain unclear. The human Posner task, a classic attention orienting paradigm, was recently adapted for use with mice, supporting the investigation of the neurobiological underpinnings of atypical attention orienting in preclinical mouse models. Objective The current study tested mice expressing the autism-associated R451C gene mutation in neuroligin-3 (NL3) on the mouse-Posner (mPosner) task. Methods NL3 R451C and wild-type (WT) mice were trained to respond to a validly or invalidly cued target on a touchscreen. The cue was a peripheral non-predictive flash in the exogenous task and a central spatially predictive image in the endogenous task. The effects of dopaminergic- and noradrenergic-modulating drugs, methylphenidate and atomoxetine, on task performance were assessed. Results In both tasks, mice were quicker and more accurate in the validly versus invalidly cued trials, consistent with results in the human Posner task. NL3 R451C and WT mice showed similar response times and accuracy but responded differently when treated with methylphenidate and atomoxetine. Methylphenidate impaired exogenous attention disengagement in NL3 R451C mice but did not significantly affect WT mice. Atomoxetine impaired endogenous orienting in WT mice but did not significantly affect NL3 R451C mice. Conclusions NL3 R451C mice demonstrated intact attention orienting but altered responses to the pharmacological manipulation of the dopaminergic and noradrenergic networks. These findings expand our understanding of the NL3 R451C mutation by suggesting that this mutation may lead to selective alterations in attentional processes.