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首页> 外文会议>Annual International Conference of the IEEE Engineering in Medicine and Biology Society >Cholinergic Modulation of CA1 Pyramidal Cells via M1 Muscarinic Receptor Activation: A Computational Study at Physiological and Supraphysiological Levels
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Cholinergic Modulation of CA1 Pyramidal Cells via M1 Muscarinic Receptor Activation: A Computational Study at Physiological and Supraphysiological Levels

机译：通过M1毒蕈碱受体激活对CA1锥体细胞的胆碱能调节：生理和超生理水平的计算研究。

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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.
机译：海马从基底前脑接受广泛的胆碱能调节，这已显示出在注意力，学习和突触可塑性中的重要作用。这种调节的中断与包括阿尔茨海默氏病在内的多种神经疾病有关。海马CA1区的金字塔形细胞在整个细胞形态中的不同位置表达几种胆碱能受体类型。开发这些细胞及其调制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，我们实施了分布最广泛的受体类型（M1毒蕈碱受体）的动力学模型，并研究了其在激发CA1锥体细胞隔室模型中的作用。我们证明，提出的模型复制了在实验结果中看到的增加的锥体细胞兴奋性。然后，我们使用该模型复制有机磷酸盐的作用，有机磷酸盐是一类农药和化学武器，其作用在于抑制乙酰胆碱的水解。我们证明了增加乙酰胆碱浓度对锥体细胞兴奋性的影响。我们实施的细胞模型及其相关的调控机制构成了在生理和超生理水平下探索海马体大规模网络模型中胆碱能调控效应的基础。

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