The function of SCN2A in neocortex

标题：SCN2A在自闭症谱系障碍中的作用 项目摘要：通过外显子组测序鉴定的突变表明， 钠通道SCN 2A与自闭症谱系障碍密切相关。SCN2A 编码神经元钠通道NaV1.2，其在动作电位位点表达 入会仪式最近，我们发现这些通道可能表达了 在整个新皮层兴奋性神经元树突，他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 电生理学、双光子成像和房室模型，以确定 Scn2a的杂合和纯合功能丧失影响了 神经元此外，我们将使用新的小鼠模型和遗传技术来询问是否 Scn2a表达水平在特定细胞类别和发育阶段的变化改变了 神经元功能这项研究的结果将提供关键的洞察力，如何突变的SCN 2A 导致自闭症谱系障碍和大脑皮层的活动依赖性发育 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.