Cognitive dysfunction including disrupted behavioral flexibility is central to neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). A cognitive measure that assesses relational memory, and the ability to flexibly assimilate and transfer learned information is transitive inference. Transitive inference is highly conserved across vertebrates and disrupted in cognitive disorders. Here, we examined how mutations in the synaptic cell-adhesion molecule neuroligin-3 (Nlgn3) that have been documented in ASD impact relational memory and behavioral flexibility. We first refined a rodent touchscreen assay to measure visual transitive inference, then assessed two mouse models of Nlgn3 dysfunction (Nlgn3 -/y and Nlgn3 R451C). Deep analysis of touchscreen behavioral data at a trial level established we could measure trajectories in flexible responding and changes in processing speed as cognitive load increased. We show that gene mutations in Nlgn3 do not disrupt relational memory, but significantly impact flexible responding. Our study presents the first analysis of reaction times in a rodent transitive inference test, highlighting response latencies from the touchscreen system are useful indicators of processing demands or decision-making processes. These findings expand our understanding of how dysfunction of key components of synaptic signaling complexes impact distinct cognitive processes disrupted in neurodevelopmental disorders, and advance our approaches for dissecting rodent behavioral assays to provide greater insights into clinically relevant cognitive symptoms.

中文翻译：

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在视觉传递推理的触摸屏测试中，雄性小鼠中Neuroligin-3的突变会影响行为灵活性，但不会影响关系记忆。

认知功能障碍（包括行为灵活性受损）对于神经发育障碍（例如自闭症谱系障碍（ASD））至关重要。评估关系记忆以及灵活吸收和转移所学信息的能力的认知措施是传递推理。传递推论在整个脊椎动物中高度保守，并且在认知障碍中受到干扰。在这里，我们检查了ASD中已记录的突触细胞粘附分子Neuroligin-3（Nlgn3）中的突变如何影响关系记忆和行为灵活性。我们首先完善了啮齿动物触摸屏测定法，以测量视觉传递推理，然后评估了两种Nlgn3功能障碍的小鼠模型（Nlgn3- / y和Nlgn3 R451C）。在试验级别上对触摸屏行为数据进行深入分析，可以确定灵活响应中的轨迹以及随着认知负荷的增加处理速度的变化。我们表明，Nlgn3中的基因突变不会破坏关系记忆，但会显着影响灵活响应。我们的研究提出了对啮齿类动物传递推理测试中反应时间的首次分析，强调了触摸屏系统的响应延迟是处理需求或决策过程的有用指标。这些发现扩大了我们对突触信号复合物关键成分功能障碍如何影响神经发育障碍中破坏的独特认知过程的理解，