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

• 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
• 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

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.

兴奋和抑制之间的平衡对皮层回路功能至关重要，因此对大脑表征的形成至关重要。此外，从癫痫到自闭症和精神分裂症等神经系统疾病也发现了失衡。皮层抑制性中间神经元是多种不同类型的细胞，它们在突触后神经元的解剖靶向、形态和分子特征上都有所不同。初级视觉皮层（V1）是研究皮层回路如何处理信息的一个很好的模型系统，因为简单的视觉刺激可以用来描述每个细胞的选择性反应特性。定向调节是V1细胞的一个重要特性，但我们仍然不知道这种选择性是如何产生的。一种理论认为，皮质内连接，由具有相似性质的细胞之间的周期性兴奋性连接和抑制性相互作用提供，抑制了对所有方向的反应，对于改进这种选择性至关重要。