Cell-specific circuits in visual cortex

视觉皮层中的细胞特异性电路

• 批准号: 7736163
• 负责人: MRIGANKA SUR
• 金额: $ 42万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7736163
• 关键词: Address; Area; Arts; Biological Neural Networks; Calcium; Calcium Signaling; Cells; Characteristics; Dendrites; Development; Disease; Dyes; Engineering; Exhibits; Ferrets; Fluorescence Resonance Energy Transfer; Fluorescent Probes; Frequencies; Functional disorder; Genetic; Genetically Engineered Mouse; Image; Individual; Injection of therapeutic agent; Interneuron function; Interneurons; Intervention; Label; Length; Location; Maps; Motion; Mus; Neurons; Parvalbumins; Population; Process; Property; Resolution; Role; Signal Transduction; Specificity; Stream; Sum; System; Tracer; V1 neuron; Vision; Visual Cortex; Visual system structure; Whole-Cell Recordings; area V1; area striata; calcium indicator; calretinin; cell type; cellular imaging; excitatory neuron; in vivo; inhibitory neuron; neural circuit; neuronal cell body; novel; optical imaging; public health relevance; response; tool; two-photon; vector; visual stimulus; Address; Area; Arts; Biological Neural Networks; Calcium; Calcium Signaling; Cells; Characteristics; Dendrites; Development; Disease; Dyes; Engineering; Exhibits; Ferrets; Fluorescence Resonance Energy Transfer; Fluorescent Probes; Frequencies; Functional disorder; Genetic; Genetically Engineered Mouse; Image; Individual; Injection of therapeutic agent; Interneuron function; Interneurons; Intervention; Label; Length; Location; Maps; Motion; Mus; Neurons; Parvalbumins; Population; Process; Property; Resolution; Role; Signal Transduction; Specificity; Stream; Sum; System; Tracer; V1 neuron; Vision; Visual Cortex; Visual system structure; Whole-Cell Recordings; area V1; area striata; calcium indicator; calretinin; cell type; cellular imaging; excitatory neuron; in vivo; inhibitory neuron; neural circuit; neuronal cell body; novel; optical imaging; public health relevance; response; tool; two-photon; vector; visual stimulus

DESCRIPTION (provided by applicant): Distinct cell types in the visual cortex contribute in unique ways to cortical circuits and function. Furthermore, the location of cortical cells within maps enables them to have specific functions. We propose to use state-of-the-art tools to examine the role of specific cell types in visual cortex circuits in vivo. First, we will examine how neurons in ferret visual cortex simultaneously map multiple response features at single cell resolution, using two-photon imaging of calcium signals. We hypothesize that neuronal representations maximize continuity and coverage by creating precise representations of response features that contain spatially offset regions of high and low rates of change. Second, we will examine the response characteristics and mappings of neuronal populations which project to specific cortical targets. We will use retrograde labeling of fluorescent tracers combined with two-photon imaging to compare response features and representations of neurons that project to area PSS, and hence to a putative motion-processing stream, with neurons that project to area 21, and hence to a putative form- processing stream. Third, we will compare the responses of inhibitory neuron subpopulations in ferret V1 recorded with high resolution imaging in vivo and subsequently identified by immunohistochemical markers ex vivo, and examine the hypothesis that specific inhibitory neuron subsets have distinct response features and tuning. We will examine the response features of inhibitory neuron subpopulations in mouse V1 marked by a genetic cre-lox system, and examine the hypothesis that parvalbumin- and calretinin-expressing interneurons have distinct response properties. In addition, we will examine the function of these interneuron types in mice with selective genetic deletion of one subpopulation or the other, in which we predict particular influences on response features of excitatory neurons. Fourth, we will examine whether individual neuronal dendrites show integrative responses, which are summed and thresholded at the soma to impart unique responses to neurons. We will examine response features of individual dendrites and dendritic compartments of single neurons in ferret V1 that have specific projections such as to area PSS and area 21. We will examine their dendritic responses by labeling with either (a) intracellular injection of calcium indicator dye, or (b) a novel genetically engineered CaMKII1 FRET probe, and compare responses to those at the soma recorded by visualized whole-cell patch recording. Together, we expect these studies to contribute significantly to an understanding of how specific cell types in visual cortex contribute to cortical function, and thus how cortical dysfunction might arise from diseases that target a particular type of cell. PUBLIC HEALTH RELEVANCE: Significance Distinct populations of neurons contribute to the development and function of neural circuits for vision; the precise organization of these cell populations and integration of their inputs within cortical area V1 is necessary for the establishment of coherent internal representations of visual stimuli. This project aims to explore the integrative properties of visual cortex on spatial scales ranging from individual dendrites to neural networks, identifying vectors of visual system dysfunction and targets for their intervention.

描述（由申请人提供）：视觉皮层中的不同细胞类型以独特的方式促进皮质电路和功能。此外，地图中皮质细胞的位置使它们具有特定的功能。我们建议使用最先进的工具来检查特定细胞类型在体内视觉皮层电路中的作用。首先，我们将使用钙信号的两光子成像在单细胞分辨率下同时绘制雪貂视觉皮层中的神经元如何同时映射多个响应特征。我们假设神经元表示通过创建包含较高变化率和低变化率的空间区域的响应特征的精确表示，从而最大程度地提高了连续性和覆盖范围。其次，我们将研究神经元种群的响应特征和映射，这些神经元群体投射到特定的皮质靶标。我们将使用荧光示踪剂与两光子成像结合的逆行标记，比较将投影到PSS区域的神经元的响应特征和表示，从而比较了推定的运动处理流，以及将神经元与21区域的神经元进行比较，从而将其投影到21区，因此与推定的形式处理流相比。第三，我们将比较在体内高分辨率成像记录的雪貂V1中抑制性神经元亚群的反应，随后通过免疫组织化学标志物在体内鉴定，并检查了特定抑制性神经元亚群具有不同的响应特征和调谐的假说。我们将检查以遗传CRE-LOX系统标记的小鼠V1中抑制性神经元亚群的响应特征，并研究了表达白蛋白素和表达钙蛋白素的中间神经元具有独特的响应特性的假设。此外，我们将检查这些中间类型的小鼠中具有选择性遗传缺失或另一个亚群的遗传缺失的功能，其中我们预测了对兴奋性神经元反应特征的特殊影响。第四，我们将检查单个神经元树突是否显示综合响应，这些反应是在SOMA上概括和阈值以赋予神经元的独特反应。我们将检查Ferret V1中单个神经元的单个树突和树突隔室具有特定预测的响应特征，这些预测（例如面积PSS和区域21）。我们将通过标记（a）（a）通过（a）通过（a）通过（a）通过对这些遗传学的camkii-freet proce probare to tublesemece probare probare probare probare proins，（a）标记的camkii1 freet probae，以及（a）通过标记来检查它们的树突状反应。 记录。我们共同期望这些研究对视觉皮质中特定细胞类型的理解有显着贡献，从而导致皮质功能，从而导致皮质功能障碍是如何源于针对特定类型细胞的疾病。公共卫生相关性：显着性不同的神经元种群有助于神经回路的发展和功能；这些细胞群体的精确组织及其在皮质区域内的输入的整合对于建立视觉刺激的连贯内部表示是必要的。该项目旨在探索视觉皮层在从单个树突到神经网络等空间尺度上的综合性能，识别视觉系统功能障碍的向量以及其干预的目标。