The role of inhibition in the mapping and plasticity of representations in V1

抑制在 V1 表征的映射和可塑性中的作用

基本信息

批准号：
8120469
负责人：
Caroline Anne Runyan
金额：
$ 4万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8120469
关键词：
Autistic Disorder Biological Models Brain Cells Clinical D Cells Data Dendrites Development Dimensions Disease Environment Epilepsy Equilibrium Exposure to Felis catus Frequencies Functional Imaging Generations Genetic Genetically Engineered Mouse Individual Interneurons Knock-in Mouse Label Maintenance Mammals Maps Measures Methods Microelectrodes Modeling Molecular Profiling Morphology Mus Neurons Optics Parvalbumins Pattern Phase Population Primates Process Property Proteins Recurrence Reporter Research Personnel Resolution Role Schizophrenia Somatostatin Specific qualifier value Stimulus Synapses Techniques Technology Transgenic Organisms Translating V1 neuron Visual Visual Cortex area striata base blind calretinin cell type excitatory neuron improved in vivo information processing inhibitory neuron nervous system disorder neuronal cell body novel strategies orientation selectivity preference receptive field response theories visual map visual receptive field visual stimulus

项目摘要

The balance between excitation and inhibition is critical to cortical circuit function, and thus to the formation of representations in the brain. Furthermore, imbalances have been discovered in neurological disorders ranging from epilepsy to autism and schizophrenia. Cortical inhibitory interneurons are a diverse class of many distinct cell types, which differ in their anatomical targeting of the post-synaptic neuron, in their morphologies, and in their molecular signatures. The primary visual cortex (V1) is an excellent model system for studying how cortical circuits process information, because simple visual stimuli can be used to describe the selective response properties of each cell. Orientation tuning is an important property of cells in V1, but we still do not know how this selectivity arises. One theory is that intracortical connections, provided by recurrent excitatory connections between cells with similar properties and inhibitory interactions, which suppress responses to all orientations, are critical for refining this selectivity. I plan to study how two types of inhibition, soma-targeting and dendritic targeting, are involved in the formation and maintenance of visual representations in the primary visual cortex of the mouse. I will use newly available genetic approaches to specifically label three subtypes of inhibitory cells, soma-targeting parvalbumin-positive (PV+), dendrite-targeting calretinin-positive (CR+), and dendrite-targeting somatostatin- positive cells (SOM+). I expect that these two types of inhibition will demonstrate unique orientation properties, that soma-targeting PV+ cells will have sharp tuning, which would allow them to provide highly specified feedforward inhibition, and that the dendrite targeting CR+ and SOM+ cells will have broad or flat tuning, allowing them to enhance the contrast-independence of orientation tuning. In the final phase of this project, I will explore the plasticity of these specific subtypes of cells, with the hypothesis that PV+ cells will demonstrate higher levels of short-term plasticity than the other two cells types.

激发与抑制之间的平衡对于皮质回路功能至关重要，因此对于大脑中表示形成至关重要。此外，在从癫痫到自闭症和精神分裂症的神经系统疾病中发现了失衡。皮质抑制性中间神经元是多种不同的细胞类型的各种类别，它们的解剖学靶向后突触神经元，形态和分子特征在于。主要的视觉皮层（V1）是研究皮质电路如何处理信息的出色模型系统，因为简单的视觉刺激可用于描述每个单元的选择性响应特性。定向调整是V1中细胞的重要特性，但我们仍然不知道这种选择性是如何产生的。一种理论是，具有相似特性和抑制性相互作用的细胞之间的复发性兴奋性连接（抑制对所有方向的响应）对于提炼这种选择性至关重要。我计划研究两种类型的抑制作用，靶向和树突状靶向如何参与小鼠主要视觉皮层中视觉表示形成和维护。我将使用新的遗传学方法来特异性标记三种亚型的抑制细胞，靶向soma靶向性白蛋白阳性（PV+），树突靶标卡氏素阳性（CR+）和树突状靶向的生；我希望这两种类型的抑制作用将证明独特的方向特性，靶向SOMA的PV+细胞将具有清晰的调整，这将使它们能够提供高度指定的进料抑制作用，并且靶向Cr+和SOM+细胞的树突将具有宽或平坦调整，允许它们增强定向调整的对比偏见。在该项目的最后阶段，我将探讨这些特定细胞亚型的可塑性，假设PV+细胞将显示出比其他两种细胞类型的短期可塑性水平更高。