Neurodevelopmental disorders (NDDs) that affect cognition, social interaction, and learning, including autism spectrum disorder (ASD) and intellectual disability (ID), have a strong genetic component. Our current understanding of risk genes highlights two main groups of dysfunction: those in genes that act as chromatin modifiers and those in genes that encode for proteins localized at or near synapses. Understanding how dysfunction in these genes contributes to phenotypes observed in ASD and ID remains a major question in neuroscience. In this review, we highlight emerging evidence suggesting that dysfunction in dendrites – regions of neurons that receive synaptic input – may be key to understanding features of neuronal processing affected in these disorders. Dendritic integration plays a fundamental role in sensory processing, cognition, and conscious perception, processes hypothesized to be impaired in NDDs. Many high-confidence ASD genes function within dendrites where they control synaptic integration and dendritic excitability. Further, increasing evidence demonstrates that several ASD/ID genes, including chromatin modifiers and transcription factors, regulate the expression or scaffolding of dendritic ion channels, receptors, and synaptic proteins. Therefore, we discuss how dysfunction of subsets of NDD-associated genes in dendrites leads to defects in dendritic integration and excitability and may be one core phenotype in ASD and ID.
Dev Neurosci

中文翻译：

---

神经发育障碍中的树突整合功能障碍


影响认知、社交和学习的神经发育障碍 (NDD)，包括自闭症谱系障碍 (ASD) 和智力障碍 (ID)，具有很强的遗传因素。我们目前对风险基因的理解强调了两类主要的功能障碍：充当染色质修饰剂的基因中的功能障碍和编码位于突触或突触附近的蛋白质的基因中的功能障碍。了解这些基因的功能障碍如何影响 ASD 和 ID 中观察到的表型仍然是神经科学中的一个主要问题。在这篇综述中，我们重点介绍了新出现的证据，表明树突（接受突触输入的神经元区域）的功能障碍可能是理解这些疾病中受影响的神经元处理特征的关键。树突整合在感觉处理、认知和意识知觉中发挥着重要作用，这些过程被假设在 NDD 中受损。许多高度可信的 ASD 基因在树突内发挥作用，控制突触整合和树突兴奋性。此外，越来越多的证据表明，一些 ASD/ID 基因，包括染色质修饰剂和转录因子，调节树突离子通道、受体和突触蛋白的表达或支架。因此，我们讨论树突中 NDD 相关基因子集的功能障碍如何导致树突整合和兴奋性缺陷，并且可能是 ASD 和 ID 的核心表型之一。
 开发神经科学