Mergenthal Adam R, Bouteiller Jean-Marie C, Berger Theodore W
Annu Int Conf IEEE Eng Med Biol Soc. 2018 Jul;2018:1396-1399. doi: 10.1109/EMBC.2018.8512574.
The hippocampus receives extensive cholinergic modulation from the basal forebrain, which has been shown to have a prominent role in attention, learning, and synaptic plasticity. Disruptions of this modulation have been linked to a variety of neural disorders including Alzheimer's Disease. Pyramidal cells of the CA1 region of the hippocampus express several cholinergic receptor types in different locations throughout the cells' morphology. Developing a computational model of these cells and their modulation provides a unique opportunity to explore how each receptor type alters the overall computational role of the cell. To this end we implemented a kinetic model of the most widely distributed receptor type, the M1 muscarinic receptor and examined its role on excitation of a compartmental model of a CA1 pyramidal cell. We demonstrate that the proposed model replicates the increased pyramidal cell excitability seen in experimental results. We then used the model to replicate the effect of organophosphates, a class of pesticides and chemical weapons, whose effects consist in inhibiting the hydrolysis of acetylcholine; we demonstrated the effect of increasing concentrations of acetylcholine on the pyramidal cell's excitability. The cell model we implemented and its associated modulation constitute a basis for exploring the effects of cholinergic modulation in a large scale network model of the hippocampus both under physiological and supraphysiological levels.
海马体接受来自基底前脑的广泛胆碱能调节，研究表明这种调节在注意力、学习和突触可塑性方面发挥着重要作用。这种调节的破坏与包括阿尔茨海默病在内的多种神经疾病有关。海马体CA1区的锥体细胞在其整个形态的不同位置表达多种胆碱能受体类型。构建这些细胞及其调节的计算模型，为探索每种受体类型如何改变细胞的整体计算作用提供了独特的机会。为此，我们实现了分布最广泛的受体类型——M1毒蕈碱受体的动力学模型，并研究了其对CA1锥体细胞房室模型兴奋的作用。我们证明，所提出的模型复制了实验结果中观察到的锥体细胞兴奋性增加的现象。然后，我们使用该模型复制了有机磷酸酯（一类杀虫剂和化学武器）的作用，其作用在于抑制乙酰胆碱的水解；我们展示了乙酰胆碱浓度增加对锥体细胞兴奋性的影响。我们构建的细胞模型及其相关调节，构成了在生理和超生理水平下探索胆碱能调节在海马体大规模网络模型中的作用的基础。
