Florey Department of Neuroscience and Mental Health - Research Publications
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ItemMice with an autism-associated R451C mutation in neuroligin-3 show a cautious but accurate response style in touchscreen attention tasks(WILEY, 2022-01)One of the earliest identifiable features of autism spectrum disorder (ASD) is altered attention. Mice expressing the ASD-associated R451C mutation in synaptic adhesion protein neuroligin-3 (NL3) exhibit impaired reciprocal social interactions and repetitive and restrictive behaviours. The role of this mutation in attentional abnormalities has not been established. We assessed attention in male NL3R451C mice using two well-established tasks in touchscreen chambers. In the 5-choice serial reaction task, rodents were trained to attend to light stimuli that appear in any one of five locations. While no differences between NL3R451C and WT mice were seen in accuracy or omissions, slower response times and quicker reward collection latencies were seen across all training and probe trials. In the rodent continuous-performance test, animals were required to discriminate, and identify a visual target pattern over multiple distractor stimuli. NL3R451C mice displayed enhanced ability to attend to stimuli when task-load was low during training and baseline but lost this advantage when difficulty was increased by altering task parameters in probe trials. NL3R451C mice made less responses to the distractor stimuli, exhibiting lower false alarm rates during all training stages and in probe trials. Slower response times and quicker reward latencies were consistently seen in NL3R451C mice in the rCPT. Slower response times are a major cognitive phenotype reported in ASD patients and are indicative of slower processing speed. Enhanced attention has been shown in a subset of ASD patients and we have demonstrated this phenotype also exists in the NL3R451C mouse model.
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ItemNo Preview AvailableMice 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(SPRINGER, 2024-03)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: NL3R451C 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. NL3R451C and WT mice showed similar response times and accuracy but responded differently when treated with methylphenidate and atomoxetine. Methylphenidate impaired exogenous attention disengagement in NL3R451C mice but did not significantly affect WT mice. Atomoxetine impaired endogenous orienting in WT mice but did not significantly affect NL3R451C mice. CONCLUSIONS: NL3R451C 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 NL3R451C mutation by suggesting that this mutation may lead to selective alterations in attentional processes.