Spatiotemporal control of dendritic inhibition by a family of diverse somatostatin-expressing interneurons

表达不同生长抑素的中间神经元家族对树突抑制的时空控制

• 批准号: 10224353
• 负责人: Bernardo Rudy
• 金额: $ 59.17万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224353
• 关键词: Acute; Affect; Anxiety Disorders; Architecture; Area; Axon; Behavior; Behavioral; Brain; Cell physiology; Cells; Cerebral cortex; Cortical Column; Dendrites; Disease; Electrophysiology (science); Epilepsy; Family; Feedback; Functional disorder; Genetic; Goals; Head; Image; Interneuron function; Interneurons; Knowledge; Label; Measures; Mediating; Mediator of activation protein; Methodology; Methods; Modality; Modeling; Morphology; Motor; Mus; Neocortex; Neurons; Neuropeptides; Output; Pathologic; Pathway interactions; Pattern; Population; Property; Pyramidal Cells; Rett Syndrome; Role; Route; Schizophrenia; Sensory; Signal Transduction; Slice; Somatosensory Cortex; Somatostatin; Source; Specificity; Structure; Synapses; Testing; Thick; Time; Touch sensation; Transgenic Mice; Vibrissae; Visual Cortex; autism spectrum disorder; awake; barrel cortex; base; cholinergic; experimental study; flexibility; hippocampal pyramidal neuron; in vivo; neocortical; novel; operation; optogenetics; response; sensory cortex; signal processing; somatosensory; sound; spatiotemporal; tool

Summary GABAergic interneurons (INs) are a diverse group of neurons with critical roles in signal processing in the cerebral cortex. Moreover, malfunction of these neurons has been implicated in a number of diseases ranging from epilepsy to schizophrenia, anxiety disorders and autism. This project is focused on the GABAergic INs that express the neuropeptide somatostatin (SST). These cells represent the second largest family of INs in the neocortex. SST INs make synapses on the dendrites of pyramidal cells (PCs) and other interneurons and have been shown to be important for dendritic integration, as well as non-linear dendritic operations, Ca2+ signaling, and plasticity. SST INs were recently suggested, based on the analysis of their patterns of in vivo activity in multiple types of sensory cortices, to be involved in a disinhibitory canonical circuit that is thought to be important in brain state-dependent control of cortical function. However, these studies have been limited to superficial cortical layers. Using a new method for the in vivo recording and labeling of genetically-tagged neurons throughout the brain we recorded for the first time from SST IN throughout the whole cortical column and discovered an unappreciated diversity of SST INs in L5/6 of somatosensory cortex. SST IN subtypes differed in the laminar distribution of their axon and had distinct patterns of in vivo activity. Taking advantage of our expanded understanding of SST IN diversity and the availability of novel genetic tools that allow the identification and manipulation of SST IN subtypes with increased specificity, the goal of this project is to test the hypothesis that SST IN subtypes differentially control the activity of specific PC dendritic branches during behavior. We will study the connectivity of L5/6 SST IN subtypes to different types of L5 PCs and determine the subcellular localization of IN synapses on the L5 PC dendrite (Aim 1). In Aim 2 electrophysiological recording, Ca2+ imaging and optogenetic manipulations will be used to investigate the function of distinct SST In subtypes on active touch responses in pyramidal cells and their cross-modal modulation by sound. Aim 3 will develop an experimentally-based model of the selective gating of information in PC dendrites mediated by SST IN subtypes. These studies will advance our understanding of SST IN function and the mechanisms of top down modulation of sensory processing.

概括 GABA能中间神经元（INS）是一组不同的神经元，在信号处理中起着关键作用 大脑皮层。此外，这些神经元的故障与多种疾病有关 从癫痫病到精神分裂症，焦虑症和自闭症。该项目的重点是Gabaergic Ins 表达神经肽生长抑素（SST）。这些细胞代表了第二大ins家族 新皮层。 SST INS在锥体细胞（PC）和其他神经元的树突上制作突触 已被证明对树突一体化以及非线性树突状作业很重要，Ca2+ 信号传导和可塑性。根据对体内模式的分析，最近建议SST INS 在多种类型的感觉皮层中的活性，参与被认为是的抑制规范电路 在大脑状态依赖性的皮质功能中很重要。但是，这些研究仅限于 浅表皮质层。使用一种新方法用于遗传标记的体内记录和标记 我们在整个皮质柱中首次从SST记录的整个大脑神经元 并在体感皮质的L5/6中发现了SST INS的不受欢迎的多样性。 SST中的子类型 其轴突的层流分布有所不同，并且具有不同的体内活性模式。利用 我们对多样性的SST的了解以及新颖的遗传工具的可用性 在特异性提高的亚型中识别和操纵SST，该项目的目的是测试 亚型中的SST差异化控制了特定PC树突分支的活性。 行为。我们将研究亚型中L5/6 SST与不同类型的L5 PC的连通性，并确定 L5 PC树突上突触中的亚细胞定位（AIM 1）。在AIM 2电生理中 记录，Ca2+成像和光遗传操作将用于研究不同SST的功能 在锥体细胞中主动触摸反应的亚型中，通过声音调制了它们的交叉模式调制。目标3 将开发一个基于实验的基于实验的信息模型的信息对PC树突中信息的选择性门控。 SST中的子类型。这些研究将提高我们对SST功能和顶部机制的理解 向下调制感官处理。