The function of SCN2A in neocortex

SCN2A在新皮质中的功能

基本信息

批准号：
10559546
负责人：
Kevin J Bender
金额：
$ 40.38万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2026-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10559546
关键词：
Action Potentials Address Adult Affect Apical Axon Back Biological Birth Calcium Cells Chromatin Remodeling Factor Complement Cre-LoxP Dendrites Development Disease Distal Electrophysiology (science)Engineering Epilepsy Etiology Family Functional disorder Future Gene Cluster Genes Genetic Techniques Glutamates Goals Heterozygote High-Throughput Nucleotide Sequencing Hippocampus Image Impairment Intellectual functioning disability Knock-in Mouse Knock-out Knowledge Life Link Loss of Heterozygosity LoxP-flanked allele Missense Mutation Modeling Mus Mutation Neocortex Neurodevelopmental Disorder Neurons Physiological Population Prefrontal Cortex Property Protein Isoforms Proteins Pyramidal Cells Recovery of Function Reporting Role SCN2A protein SCN8A gene Shapes Site Sodium Channel Synapses Synaptic plasticity Techniques Testing Therapeutic Therapeutic Intervention Time Variant Work autism spectrum disorder critical period early onset excitatory neuron exome sequencing gain of function hippocampal pyramidal neuron infancy insight interest loss of function loss of function mutation member mouse genetics mouse model neocortical neuronal excitability novel postnatal development repetitive behavior restoration social communication synaptic function two-photon voltage

项目摘要

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.

标题：SCN2A在自闭症谱系障碍中的功能项目摘要：通过外显组测序确定的突变证明了破坏钠通道SCN2A与自闭症谱系障碍密切相关。 SCN2A 编码在动作电位的位点表达的神经元钠通道NAV1.2 引发。最近，我们发现这些渠道可能是表达的在整个新皮层兴奋性神经元树突中，它们的树突功能可能是与突触成熟和可塑性有关。在这里，我们将使用电生理学，2光子成像和隔室建模，以确定如何 SCN2A功能功能的杂合和纯合损失影响的综合特性神经元。此外，我们将使用新颖的鼠标模型和遗传技术来询问是否是否 SCN2A表达水平的变化在特定的细胞类别和发育阶段的变化改变了神经元功能。这项研究的结果将为SCN2A中的突变如何提供关键的见解有助于自闭症谱系障碍和皮质的活性发展电路。