Gene network analysis reveals a role for striatal glutamatergic receptors in dysregulated risk-assessment behavior of autism mouse models

Autism Spectrum Disorder (ASD) presents a wide, and often varied, behavioral phenotype. Impulsivity and improper assessment of risks has been widely reported among individuals diagnosed with ASD. However, there is little knowledge of the molecular underpinnings of the impaired risk-assessment phenotype. In this study, we have identified impaired risk-assessment activity in multiple male ASD mouse models. By performing network-based analysis of striatal whole transcriptome data from each of these ASD models, we have identified a cluster of glutamate receptor-associated genes that correlate with the risk-assessment phenotype. Furthermore, pharmacological inhibition of striatal glutamatergic receptors was able to mimic the dysregulation in risk-assessment. Therefore, this study has identified a molecular mechanism that may underlie impulsivity and risk-assessment dysregulation in ASD. Examination of whole transcriptome in dorsal striatum of four ASD mouse models and controls自闭症谱系障碍（Autism Spectrum Disorder, ASD）具有广泛且常具异质性的行为表型。临床研究已广泛报道，确诊ASD的个体存在冲动行为与风险评估不当的问题。但目前学界对该受损风险评估表型的分子基础仍知之甚少。本研究在多个雄性ASD小鼠模型中，观测到了受损的风险评估活动。通过对各ASD模型纹状体全转录组数据开展基于网络的分析，本研究鉴定出了一个与风险评估表型相关的谷氨酸受体关联基因簇。此外，对纹状体谷氨酸能受体进行药理学抑制，可模拟风险评估失调的表型。综上，本研究鉴定出了可能介导ASD患者冲动行为与风险评估失调的分子机制。本研究对4株ASD小鼠模型及其对照的背侧纹状体开展了全转录组检测。