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: 9789070
• 负责人: Bernardo Rudy
• 金额: $ 59.18万
• 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/9789070
• 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.

总结 GABA能中间神经元（IN）是一组不同的神经元，在神经元的信号处理中起关键作用。 大脑皮层此外，这些神经元的功能障碍与许多疾病有关， 从癫痫到精神分裂症，焦虑症和自闭症。该项目的重点是GABA能IN 表达神经肽生长抑素（SST）。这些细胞代表了第二大的IN家族， 大脑皮层SST IN在锥体细胞（PC）和其他中间神经元的树突上形成突触， 已被证明是重要的树突整合，以及非线性树突的运作，钙离子 信号和可塑性。最近，基于对SST IN在体内的模式的分析，提出了SST IN。 在多种类型的感觉皮层的活动，参与了去抑制典型回路，被认为是 在大脑状态依赖的皮层功能控制中很重要。然而，这些研究仅限于 皮质浅层使用一种新的方法在体内记录和标记基因标记的 我们第一次从SST IN记录了整个大脑的神经元， 并发现L5/6躯体感觉皮层中SST INs的多样性。SST IN亚型 不同的层状分布的轴突，并有不同的模式，在体内活动。利用 我们对SST IN多样性的深入了解以及新的遗传工具的可用性， 鉴定和操作SST IN亚型，增加特异性，本项目的目标是测试 假设SST IN亚型差异控制特定PC树突状分支的活性， 行为我们将研究L5/6 SST IN亚型与不同类型L5 PC的连接，并确定 IN突触在L5 PC树突上的亚细胞定位（Aim 1）。In Aim 2电生理 本研究将利用细胞记录、Ca 2+成像和光遗传学操作等技术来研究不同SST的功能 锥体细胞主动触摸反应的亚型及其声音的跨模态调制。目标3 将开发一个基于实验的模型，在PC树突介导的信息选择性门控， SST IN亚型。这些研究将进一步加深我们对SST IN功能和TOP作用机制的认识。 感觉处理的下调。