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）肾小球层内的一类中间神经元，最近已被证明在嗅觉感觉信息的编码和处理中具有多种重要作用。 ET 细胞具有显着的动力学特征，例如以呼吸 theta 频率自发爆发，并在肾小球内表现出高度相关的活动。通过向其他局部中间神经元和主要输出神经元提供前馈激励，ET 细胞可以放大感觉输入，有助于噪声抑制，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 输出到大脑其他区域的信息。 然而，由于肾小球内部和肾小球之间突触相互作用的复杂性，以及关于 OB 电路连接性的复杂且有时相互矛盾的实验数据，对 ET 细胞在嗅觉信息处理中的功能作用的透彻理解受到阻碍。在这里，我提出了一种计算建模方法来识别 ET 细胞的协调动力学机制，并评估它们对嗅觉信息编码和处理的贡献 - 这是生物物理现实计算模型擅长的任务。具体来说，我建议基于广泛发表的生理数据并受其约束，逐步构建 OB 的生物物理细胞和网络模型。首先将开发 ET 细胞和单肾小球网络的细胞模型，并通过实验数据进行审查。然后，这些模型将被整合到一个多肾小球网络模型中，该模型结合了肾小球间相互作用和更深的 OB 电路，以研究 ET 细胞在生成和协调全局 OB 振荡动力学中的动态作用。这种将复杂数据集系统、定量地整合到单一框架中对于全面理解 ET 细胞功能至关重要，并将产生可通过实验检验的预测。