Department of Psychology, Yale University, New Haven, CT 06520, USA; Department of Molecular, Cellular, Developmental Biology, New Haven, CT 06520, USA.
Department of Psychology, Yale University, New Haven, CT 06520, USA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.
Neurosci Biobehav Rev. 2022 Oct;141:104803. doi: 10.1016/j.neubiorev.2022.104803. Epub 2022 Jul 29.
Although Autism Spectrum Disorder (ASD) is increasing in diagnostic prevalence, treatment options are inadequate largely due to limited understanding of ASD's underlying neural mechanisms. Contributing to difficulties in treatment development is the vast heterogeneity of ASD, from physiological causes to clinical presentations. Recent studies suggest that distinct genetic and neurological alterations may converge onto similar underlying neural circuits. Therefore, an improved understanding of neural circuit-level dysfunction in ASD may be a more productive path to developing broader treatments that are effective across a greater spectrum of ASD. Given the social preference behavioral deficits commonly seen in ASD, dysfunction in circuits mediating social preference may contribute to the atypical development of social cognition. We discuss some of the animal models used to study ASD and examine the function and effects of dysregulation of the social preference circuits, notably the medial prefrontal cortex-amygdala and the medial prefrontal cortex-nucleus accumbens circuits, in these animal models. Using the common circuits underlying similar behavioral disruptions of social preference behaviors as an example, we highlight the importance of identifying disruption in convergent circuits to improve the translational success of animal model research for ASD treatment development.
尽管自闭症谱系障碍 (ASD) 的诊断患病率在不断增加，但治疗选择仍然不足，这主要是由于对 ASD 潜在神经机制的理解有限。导致治疗开发困难的原因是 ASD 的巨大异质性，从生理原因到临床表现。最近的研究表明，不同的遗传和神经改变可能集中在相似的潜在神经回路上。因此，对 ASD 中神经回路功能障碍的深入了解可能是开发更广泛治疗方法的更有效途径，这些方法在更广泛的 ASD 谱系中有效。鉴于 ASD 中常见的社交偏好行为缺陷，介导社交偏好的回路功能障碍可能导致社交认知的异常发展。我们讨论了一些用于研究 ASD 的动物模型，并研究了调节社交偏好回路的功能和影响，特别是内侧前额叶皮层-杏仁核和内侧前额叶皮层-伏隔核回路，在这些动物模型中的作用。我们以共同的社交偏好行为的相似行为中断的潜在回路为例，强调了识别中断的收敛回路的重要性，以提高 ASD 治疗开发的动物模型研究的转化成功率。
