Dynamical Mechanisms of External Tufted Cells in Olfactory Information Processing

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，最近已显示其在嗅觉感觉信息的编码和处理中具有多种重要作用。ET细胞具有显著的动力学特征，如在呼吸θ频率下自发爆发，并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要输出神经元提供前馈兴奋，ET细胞可以放大感觉输入，有助于噪声抑制，并充当网络起搏器，同步肾小球输出并调节更深OB电路的动力学，所述更深OB电路确定从OB输出到大脑其他区域的信息。 然而，由于肾小球内和肾小球间突触相互作用的复杂性以及OB电路连接性的复杂且有时相互矛盾的实验数据，阻碍了对ET细胞在嗅觉信息处理中的功能作用的深入了解。在这里，我提出了一个计算建模方法，以确定协调的ET细胞的动力学机制，并评估其贡献的编码和处理的嗅觉信息-一项任务，在生物病理学现实的计算建模擅长。具体来说，我提出了一个逐步建设的生物物理细胞和网络模型的OB，广泛发表的生理数据的基础上和约束。ET细胞和单肾小球网络的细胞模型将首先开发，并通过实验数据进行验证。然后，这些模型将被整合到一个多肾小球网络模型，将肾小球间的相互作用和更深的OB电路，以研究ET细胞在产生和协调全球OB振荡动力学的动态作用。这种将复杂数据集系统和定量整合到一个单一框架中的方法对于综合理解ET细胞功能至关重要，并将产生实验可检验的预测。

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.