Dynamical Mechanisms of External Tufted Cells in Olfactory Information Processing

外部簇状细胞嗅觉信息处理的动力学机制

• 批准号: 9172652
• 负责人: GUOSHI LI
• 金额: $ 15.2万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9172652
• 关键词: Alpha Cell; Attention; Axon; Biological; Biophysics; Brain; Brain region; Breathing; Cell model; Cell physiology; Cells; Characteristics; Clinical; Code; Complex; Computer Simulation; Consensus; Data; Data Set; Elements; Employee Strikes; Exhibits; Feedback; Frequencies; Glutamates; Impairment; Interneurons; Intervention; Investigation; Lateral; Mediating; Modeling; Neurologic; Neurons; Noise; Odors; Output; Pacemakers; Pathology; Pattern; Periodicity; Pharmacology; Physiological; Play; Positioning Attribute; Publishing; Respiration; Role; Route; Sensory; Shapes; Site; Synapses; System; Testing; base; biophysical model; granule cell; information processing; mitral cell; network models; novel; olfactory bulb; public health relevance; relating to nervous system; respiratory; response; sensory input; signal processing

DESCRIPTION (provided by applicant): External tufted (ET) cells are a class of interneuron within the glomerular layer of the olfactory bulb (OB) that recently have been shown to have multiple important roles in the coding and processing of olfactory sensory information. ET cells possess striking dynamical characteristics such as spontaneous bursting at respiratory theta frequency and exhibit highly correlated activity within a glomerulus. By providing feedforward excitation to other local interneurons and to principal output neurons, ET cells may amplify sensory input, contribute to noise suppression, and act as network pacemakers, synchronizing glomerular output and regulating the dynamics of deeper OB circuitry that determine the information exported from the OB to other regions of the brain. A thorough understanding of the functional role of ET cells in olfactory information processing is hindered, however, both by the complexity of synaptic interactions within and among glomeruli and by intricate and sometimes contradictory experimental data regarding the connectivity of OB circuitry. Here, I propose a computational modeling approach to identify the coordinated dynamical mechanisms of ET cells and assess their contributions to the encoding and processing of olfactory information - a task at which biophysically realistic computational modeling excels. Specifically, I propose a step-by-step construction of biophysical cellular and network models of the OB, based on and constrained by extensive published physiological data. Cellular models of ET cells and single-glomerular networks will be developed first, and vetted by experimental data. These models then will be integrated into a multiglomerular network model incorporating interglomerular interactions and deeper OB circuitry to investigate the dynamical role of ET cells in generating and coordinating global OB oscillatory dynamics. This systematic and quantitative integration of complex datasets into a single framework is essential for an integrated understanding of ET cell function, and will produce experimentally testable predictions.

描述（由申请人提供）：外部簇状（ET）细胞是嗅球（OB）（OB）的肾小球层中的一类神经元，最近已被证明在嗅觉感觉信息的编码和处理中具有多个重要作用。 ET细胞具有惊人的动力学特征，例如在呼吸道theta频率下自发爆发，并且在肾小球内表现出高度相关的活性。通过向其他局部中间神经元和主输出神经元提供前馈激发，ET细胞可以扩增感觉输入，有助于抑制噪声，并充当网络起搏器，同步肾小球输出并调节更深的OB电路的动态，从而确定从OB到其他大脑的其他区域导出的信息。 然而，彻底了解ET细胞在嗅觉信息处理中的功能作用受到阻碍，但是，由于肾小球内部和肾小球之间的突触相互作用的复杂性以及有关OB电路连通性的复杂，有时甚至是矛盾的实验数据。在这里，我提出了一种计算建模方法，以识别ET细胞的协调动力学机制，并评估它们对嗅觉信息的编码和处理的贡献 - 生物物理上现实的计算建模卓越的任务。具体而言，我提出了OB的生物物理细胞和网络模型的分步构建，并受到广泛发表的生理数据的约束。 ET细胞和单胶质网络的细胞模型将首先开发，并通过实验数据进行审查。然后，这些模型将集成到结合层间相互作用和更深入的OB电路的多数层网络模型中，以研究ET细胞在生成和协调全局OB振荡动力学中的动力学作用。将复杂数据集纳入单个框架的系统和定量集成对于对ET细胞功能的整合理解至关重要，并且将产生可实验测试的预测。