Tobin Anne-Elise, Van Hooser Stephen D, Calabrese Ronald L
Department of Biology, Emory University, Atlanta, GA 30322, USA.
J Neurophysiol. 2006 Oct;96(4):2107-20. doi: 10.1152/jn.00026.2006. Epub 2006 Jun 7.
Conductance-based neuron models aid in understanding the role intrinsic and synaptic currents play in producing neuronal activity. Incorporating morphological detail into a model allows for additional analysis of nonhomogeneous distributions of active and synaptic conductances, as well as spatial segregation of electrical events. We developed a morphologically detailed "Full Model" of a leech heart interneuron that replicates reasonably well intracellular recordings from these interneurons. However, it constitutes hundreds of compartments, each increasing parameter space and simulation time. To reduce the number of compartments of the Full Model, while preserving conductance densities and distributions, its compartments were grouped into functional groups that each share identical conductance densities. Each functional group was sequentially reduced to one or two compartments, preserving surface area, conductance densities, and its contribution to input resistance. As a result, the input resistance and membrane time constant were preserved. The axial resistances of several compartments were rescaled to match the amplitude of synaptic currents and low-threshold calcium currents and the shape of action potentials to those in the Full Model. This reduced model, with intrinsic conductances, matched the activity of the Full Model for a variety of simulated current-clamp and voltage-clamp data. Because surface area and conductance distribution of the functional groups of the Full Model were maintained, parameter changes introduced into the reduced model can be directly translated to the Full Model. Thus our computationally efficient reduced morphology model can be used as a tool for exploring the parameter space of the Full Model and in network simulations.
基于电导的神经元模型有助于理解内在电流和突触电流在产生神经元活动中所起的作用。将形态学细节纳入模型可以对有源电导和突触电导的非均匀分布以及电事件的空间分离进行额外分析。我们开发了一种水蛭心脏中间神经元的形态学详细“完整模型”，该模型能够较好地复制这些中间神经元的细胞内记录。然而，它由数百个隔室组成，每个隔室都会增加参数空间和模拟时间。为了减少完整模型的隔室数量，同时保留电导密度和分布，其隔室被分组为功能组，每个功能组共享相同的电导密度。每个功能组依次减少到一两个隔室，同时保留表面积、电导密度及其对输入电阻的贡献。结果，输入电阻和膜时间常数得以保留。对几个隔室的轴向电阻进行重新缩放，以使突触电导和低阈值钙电流的幅度以及动作电位的形状与完整模型中的相匹配。这个具有内在电导的简化模型，对于各种模拟的电流钳和电压钳数据，都与完整模型的活动相匹配。由于完整模型功能组的表面积和电导分布得以保留，引入简化模型的参数变化可以直接转化到完整模型中。因此，我们这个计算效率高的简化形态学模型可以用作探索完整模型参数空间以及进行网络模拟的工具。
