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CRCNS: Higher-order feature detection in olfactory bulb

CRCNS：嗅球中的高阶特征检测

基本信息

批准号：
8523031
负责人：
Thomas A Cleland
金额：
$ 21.15万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8523031
关键词：
Action Potentials Address Affect Afferent Neurons Alzheimer&apos s Disease American Animals Apical Architecture Area Behavioral Binding Calcium Cells Characteristics Charge Collaborations Communication Competence Complex Computer Simulation Computer-Assisted Image Analysis Cytoplasmic Granules Dementia Dendrites Dependence Diagnostic Failure German population Halorhodopsins Image Individual Institution Interneurons Investigation Laboratories Lateral Learning Measures Mediating Memory Modeling Mus Neurons Odors Optics Outcome Output Pattern Perception Plastics Positioning Attribute Postdoctoral Fellow Process Psychophysics Receptor Activation Recording of previous events Recurrence Research Research Personnel Retina Slice Sodium Specificity Stimulus Structure Students Synapses System Techniques Testing Theoretical model Time Training Transgenic Mice Travel Visual Visual system structure Whole-Cell Recordings Woman Work analog area striata base granule cell neuronal cell body olfactory bulb operation optical imaging optogenetics receptive field receptor regenerative research study response spatiotemporal success theories

项目摘要

DESCRIPTION (provided by applicant): Reciprocal interactions between mitral and granule cells in the olfactory bulb external plexiform layer (EPL) modify the timing of mitral cell action potentials and thereby influence the information that the olfactory bulb exports to its multiple targets. Theoretical and experimental results produced by each of the two collaborating PIs of this proposal have shown that this powerful and plastic EPL network is not responsible for the simple "contrast-enhancement" function often attributed to it (instead, this largely occurs in the glomerular layer). Rather, EPL interactions perform additional, subsequent operations on odor representations that mediate changes in odor perception and representation based in part on an individual animal's history of odor learning. Specifically, we here propose that computations in the EPL serve to render mitral cell output patterns selective for certain higher-order features of odors in the same sense that neurons in primary visual cortex are selective for higher-order visual features such as edge and orientation - that is, they reflect the co-activation of certain spatiotemporal combinations of receptors that together are characteristic of a meaningful odor. We here propose to develop detailed theoretical models of this hypothesis and its implications and to test its main critical predictions experimentally. The model in its present form predicts (1) that whereas granule cells can be excited by mitral cell lateral dendrites irrespective of their physical proximity, spike timing in mitral cells is affected only by inhibition from physically neighboring granule cells, and (2) that granule cells require the simultaneous activation of specific sets of afferent (glomerular) inputs in order to evoke a whole-cell regenerative response and thereby evoke lateral inhibition. This architecture has substantial implications for the processing of odor representations that we will develop in Aim 1. To test this model, we will determine whether granule cell effects on mitral cell activity depend on physical proximity using spatially selective optogenetic activation and silencing of granule cells (Aim 2), measure the form and specificity of the afferent activity patterns required to evoke spikes in granule cells using optical stimulation of olfactory bulb glomeruli (Aim 3), and test the model's assumptions regarding the structure of olfactory bulb plasticity by measuring the perceptual effects of competing odor representations (Aim 4). The intellectual merit of this application derives from its use of state-of-the-art computational modeling to structure the proposed experiments and interpret their results, along with the use of newly-developed experimental techniques to address the longstanding questions about EPL function and processing that the theory described herein has framed and rendered testable. The collaboration between PIs Cleland and Schaefer is essential to the success of this proposal, as PI Schaefer's experimental techniques are uniquely able to test the prediction of PI Cleland's theoretical models. The efficiency of this collaboration is enhanced by the cross-competence of the PIs: PI Schaefer is competent in both computational and behavioral approaches and utilizes both in his research, whereas PI Cleland is competent in electrophysiological approaches and utilizes them in his research. This collaboration will benefit students and postdocs at both institutions by integrating them into a genuinely interdisciplinary framework encompassing both experimental and computational approaches, and facilitating their cross-training by enabling travel between labs. Consequently, the broader impacts of this proposal include the cross-training of students from diverse backgrounds in coordinated theoretical and experimental techniques as well as exposing them to both American and German laboratories. Both PIs have a strong history of training undergraduates and women in areas in which women remain underrepresented. This proposal also provides for the substantial participation of undergraduate researchers.

描述（由申请人提供）：嗅球外部丛状层（EPL）中的二尖瓣和颗粒细胞之间的相互作用改变了二尖瓣细胞动作电位的时间，从而影响嗅球向其多个目标输出的信息。该提案的两个合作 PI 各自产生的理论和实验结果表明，这种强大且可塑的 EPL 网络并不负责通常归因于其的简单“对比度增强”功能（相反，这主要发生在肾小球层中）。相反，EPL 交互对气味表征执行额外的后续操作，部分基于个体动物的气味学习历史来调节气味感知和表征的变化。具体来说，我们在这里提出，EPL 中的计算有助于使二尖瓣细胞输出模式对气味的某些高阶特征具有选择性，就像初级视觉皮层中的神经元对边缘和方向等高阶视觉特征具有选择性一样，也就是说，它们反映了受体的某些时空组合的共同激活，这些受体一起构成了有意义的气味的特征。我们在此建议开发该假设及其含义的详细理论模型，并通过实验检验其主要关键预测。目前形式的模型预测：（1）尽管颗粒细胞可以被二尖瓣细胞侧向树突兴奋，无论它们的物理距离如何，但二尖瓣细胞中的尖峰时间仅受到物理邻近颗粒细胞的抑制的影响，以及（2）颗粒细胞需要同时激活特定的传入（肾小球）输入组才能唤起全细胞再生反应，从而引起侧抑制。这种架构对我们将在目标 1 中开发的气味表征的处理具有重大意义。为了测试这个模型，我们将使用颗粒细胞的空间选择性光遗传学激活和沉默来确定颗粒细胞对二尖瓣细胞活动的影响是否依赖于物理接近度（目标 2），使用嗅球的光学刺激来测量在颗粒细胞中引起尖峰所需的传入活动模式的形式和特异性肾小球（目标 3），并通过测量竞争性气味表征的感知效果来测试模型关于嗅球可塑性结构的假设（目标 4）。该应用程序的智力优点源于其使用最先进的计算模型来构建所提出的实验并解释其结果，以及使用新开发的实验技术来解决有关 EPL 功能和处理的长期存在的问题，本文描述的理论已经框架并使其可测试。 PI Cleland 和 Schaefer 之间的合作对于该提案的成功至关重要，因为 PI Schaefer 的实验技术具有独特的能力来测试 PI Cleland 理论模型的预测。 PI 的交叉能力提高了这种合作的效率：PI Schaefer 擅长计算和行为方法，并在他的研究中运用这两种方法，而 PI Cleland 擅长电生理学方法，并在他的研究中运用它们。此次合作将使两个机构的学生和博士后受益，将他们整合到一个包含实验和计算方法的真正的跨学科框架中，并通过允许实验室之间的旅行来促进他们的交叉培训。因此，该提案的更广泛影响包括对来自不同背景的学生进行协调理论和实验技术的交叉培训，以及让他们接触美国和德国的实验室。两位 PI 都拥有在女性代表性不足的领域培训本科生和女性的悠久历史。该提案还规定本科生研究人员的实质性参与。