Lupascu Carmen A, Morabito Annunziato, Merenda Elisabetta, Marinelli Silvia, Marchetti Cristina, Migliore Rosanna, Cherubini Enrico, Migliore Michele
Institute of Biophysics, National Research Council Palermo, Italy.
European Brain Research Institute Rome, Italy.
Front Neuroinform. 2016 Jun 30;10:23. doi: 10.3389/fninf.2016.00023. eCollection 2016.
Computational modeling of brain circuits requires the definition of many parameters that are difficult to determine from experimental findings. One way to help interpret these data is to fit them using a particular kinetic model. In this paper, we propose a general procedure to fit individual synaptic events recorded from voltage clamp experiments. Starting from any given model description (mod file) in the NEURON simulation environment, the procedure exploits user-defined constraints, dependencies, and rules for the parameters of the model to fit the time course of individual spontaneous synaptic events that are recorded experimentally. The procedure, implemented in NEURON, is currently available in ModelDB. A Python version is installed, and will be soon available for public use, as a standalone task in the Collaboratory Portal of the Human Brain Project. To illustrate the potential application of the procedure, we tested its use with various sets of experimental data on GABAergic synapses; gephyrin and gephyrin-dependent pathways were chosen as a suitable example of a kinetic model of synaptic transmission. For individual spontaneous inhibitory events in hippocampal pyramidal CA1 neurons, we found that gephyrin-dependent subcellular pathways may shape synaptic events at different levels, and can be correlated with cell- or event-specific activity history and/or pathological conditions.
脑回路的计算建模需要定义许多难以从实验结果中确定的参数。帮助解释这些数据的一种方法是使用特定的动力学模型对其进行拟合。在本文中，我们提出了一种通用程序，用于拟合从电压钳实验记录的单个突触事件。从NEURON模拟环境中的任何给定模型描述（mod文件）开始，该程序利用用户定义的约束、依赖性和模型参数规则来拟合实验记录的单个自发突触事件的时间进程。该程序在NEURON中实现，目前可在ModelDB中获取。已安装Python版本，并且很快将作为人类大脑计划协作门户中的独立任务供公众使用。为了说明该程序的潜在应用，我们用关于GABA能突触的各种实验数据集测试了它的用途；选择桥连蛋白和桥连蛋白依赖性途径作为突触传递动力学模型的合适示例。对于海马锥体CA1神经元中的单个自发抑制事件，我们发现桥连蛋白依赖性亚细胞途径可能在不同水平上塑造突触事件，并且可以与细胞或事件特异性活动历史和/或病理状况相关联。
