Dynamical Mechanisms of External Tufted Cells in Olfactory Information Processing

描述（申请人提供）：外部簇状细胞（ET）是一类位于嗅球（OB）肾小球层的中间神经元，最近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细胞具有显著的动力学特征，如在呼吸θ频率下自发破裂，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，有助于抑制噪声，并充当网络起搏器，同步肾小球输出并调节更深层次OB电路的动态，该电路决定从OB输出到大脑其他区域的信息。

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.