The function of SCN2A in neocortex

标题：SCN2A 在自闭症谱系障碍中的功能 项目摘要：通过外显子组测序鉴定的突变表明， 钠通道 SCN2A 与自闭症谱系障碍密切相关。 SCN2A 编码神经元钠通道 NaV1.2，在动作电位位点表达 启动。最近，我们发现这些通道可能表达 整个新皮质兴奋性神经元树突，它们的树突功能可能是 突触成熟和可塑性的结果。在这里，我们将使用补集 电生理学、2 光子成像和房室建模以确定如何 Scn2a 杂合子和纯合子功能丧失影响整合特性 神经元。此外，我们将使用新型小鼠模型和遗传技术来探究是否 特定细胞类别和发育阶段的 Scn2a 表达水平的变化会发生变化 神经元功能。这项研究的结果将为 SCN2A 突变如何发生提供重要的见解 有助于自闭症谱系障碍和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.