Dynamical Mechanisms of External Tufted Cells in Olfactory Information Processing

描述(申请人提供)：外丛(ET)细胞是位于嗅球(OB)肾小球层的一类中间神经元，最近被证明在嗅觉信息的编码和处理中具有多种重要作用。ET细胞具有显著的动力学特征，如呼吸频率的自发爆发，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输出神经元提供前馈兴奋，ET细胞可以放大感觉输入，有助于抑制噪声，并充当网络起搏器，同步肾小球输出，调节更深层次OB回路的动力学，该回路决定从OB向大脑其他区域输出的信息。 然而，由于肾小球内和肾小球之间突触相互作用的复杂性，以及关于OB回路连接的复杂甚至有时相互矛盾的实验数据，彻底理解ET细胞在嗅觉信息处理中的功能作用是受阻的。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建模所擅长的任务。具体地说，我建议一步一步地构建OB的生物物理细胞和网络模型，基于并受到广泛发表的生理数据的约束。首先将建立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，这些模型将被集成到包含肾小球间相互作用和更深层次的OB回路的多肾小球网络模型中，以研究ET细胞在产生和协调全球OB振荡动力学中的动力学作用。将复杂的数据集系统地和定量地集成到一个单一的框架中，对于完整地理解ET细胞的功能是必不可少的，并将产生可通过实验检验的预测。

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.