Hulbert S W, Jiang Y-H
Department of Neurobiology, Duke University School of Medicine, Durham, NC 27710, United States.
Department of Neurobiology, Duke University School of Medicine, Durham, NC 27710, United States; Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, United States.
Neuroscience. 2016 May 3;321:3-23. doi: 10.1016/j.neuroscience.2015.12.040. Epub 2015 Dec 28.
Autism spectrum disorders (ASDs) present unique challenges in the fields of genetics and neurobiology because of the clinical and molecular heterogeneity underlying these disorders. Genetic mutations found in ASD patients provide opportunities to dissect the molecular and circuit mechanisms underlying autistic behaviors using animal models. Ongoing studies of genetically modified models have offered critical insight into possible common mechanisms arising from different mutations, but links between molecular abnormalities and behavioral phenotypes remain elusive. The challenges encountered in modeling autism in mice demand a new analytic paradigm that integrates behavioral assessment with circuit-level analysis in genetically modified models with strong construct validity.
自闭症谱系障碍（ASD）在遗传学和神经生物学领域带来了独特的挑战，因为这些疾病存在临床和分子异质性。在自闭症谱系障碍患者中发现的基因突变提供了利用动物模型剖析自闭症行为背后的分子和神经回路机制的机会。对转基因模型的持续研究为不同突变可能产生的共同机制提供了重要见解，但分子异常与行为表型之间的联系仍然难以捉摸。在小鼠中模拟自闭症所遇到的挑战需要一种新的分析范式，即将行为评估与具有强大构建效度的转基因模型中的神经回路水平分析相结合。
