The function of SCN2A in neocortex

SCN2A在自闭症谱系障碍中的作用 项目概述：通过外显子组测序确定的突变表明 钠通道SCN2A与自闭症谱系障碍密切相关。SCN2A 编码神经元性钠通道NaV1.2，在动作电位部位表达 入会仪式。最近，我们发现这些通道很可能表达 在新皮质兴奋性神经元树突中，它们的树突功能可能是 是突触成熟和可塑性的结果。在这里，我们将使用补语 电生理学、双光子成像和隔室模型以确定 SCN2A型杂合性和纯合性功能缺失对心绞痛综合特性的影响 神经元。此外，我们将使用新的小鼠模型和遗传技术来询问 特定细胞类别和发育阶段中SCN2A表达水平的变化会改变 神经功能。这项研究的结果将为SCN2A的突变提供关键的见解 导致自闭症谱系障碍和大脑皮质活动依赖性发育 电路。

Title: The function of SCN2A in autism spectrum disorder Project Summary: Mutations identified by exome sequencing demonstrate that disruption of the sodium channel SCN2A is strongly associated with autism spectrum disorder. SCN2A encodes the neuronal sodium channel NaV1.2, which is expressed at the site of action potential initiation. More recently, we have discovered that these channels are likely expressed throughout neocortical excitatory neuron dendrites, and that their dendritic function may be consequential to synaptic maturation and plasticity. Here, we will use a complement of electrophysiology, 2-photon imaging, and compartmental modeling to determine how heterozygous and homozygous loss of function of Scn2a affects the integrative properties of neurons. Furthermore, we will use novel mouse models and genetic techniques to ask whether changes in Scn2a expression levels in particular cell classes and developmental stages alters neuronal function. Results of this study will provide critical insight into how mutations in SCN2A contributes to autism spectrum disorder and the activity dependent development of cortical circuits.