Dysfunction in cholinergic modulation has been linked to a variety of cognitive disorders including Alzheimer’s disease. The important role of this neurotransmitter has been explored in a variety of experiments, yet many questions remain unanswered about the contribution of cholinergic modulation to healthy hippocampal function. To address this question, we have developed a model of CA1 pyramidal neuron that takes into consideration muscarinic receptor activation in response to changes in extracellular concentration of acetylcholine and its effects on cellular excitability and downstream intracellular calcium dynamics. This model incorporates a variety of molecular agents to accurately simulate several processes heretofore ignored in computational modeling of CA1 pyramidal neurons. These processes include the inhibition of ionic channels by phospholipid depletion along with the release of calcium from intracellular stores (i.e. the endoplasmic reticulum). This paper describes the model and the methods used to calibrate its behavior to match experimental results. The result of this work is a compartmental model with calibrated mechanisms for simulating the intracellular calcium dynamics of CA1 pyramidal cells with a focus on those related to release from calcium stores in the endoplasmic reticulum. From this model we also make various predictions for how the inhibitory and excitatory responses to cholinergic modulation vary with agonist concentration. This model expands the capabilities of CA1 pyramidal cell models through the explicit modeling of molecular interactions involved in healthy cognitive function and disease. Through this expanded model we come closer to simulating these diseases and gaining the knowledge required to develop novel treatments.

Adam Mergenthal

Jean-Marie C. Bouteiller

Gene J. Yu

Theodore W. Berger

Frontiers in Computational Neuroscience

FRONTIERS IN COMPUTATIONAL NEUROSCIENCE 是一本一流的电子期刊，致力于推广大脑功能的理论建模，促进理论和实验神经科学之间的跨学科互动。对大脑惊人能力的理解进展仍然有限，我们相信只有深入的理论思考和不同学科和方法之间的相互促进合作才能实现。因此，我们邀请对广泛主题的原创贡献，以展示这种合作的成果，或为未来的联盟提供刺激。我们的目标是为神经系统的前沿理论研究提供一个互动论坛，并向更广泛的神经科学界传播最好的理论研究。从生物物理驱动的神经元和突触的逼真模拟到推理和决策的高级抽象模型，各种风格和所有级别的模型都受到欢迎。虽然该杂志主要侧重于基于理论和驱动的研究，但我们欢迎验证和测试理论结论的实验研究。另外：COMP NEURO

Frontiers in Computational Neuroscience is a leading electronic journal dedicated to advancing theoretical modeling of brain functions and fostering interdisciplinary interactions between theoretical and experimental neuroscience. Our understanding of the brain's remarkable capabilities remains limited, and we believe that only through deep theoretical reflection and collaborative efforts across various disciplines and methods can we achieve breakthroughs. Therefore, we invite original contributions on a wide range of topics to showcase the results of such collaboration or to inspire future alliances. Our goal is to provide an interactive forum for cutting-edge theoretical research on the nervous system and to disseminate the best theoretical studies to the broader neuroscience community. From biophysically driven realistic simulations of neurons and synapses to advanced abstract models of reasoning and decision-making, a variety of styles and all levels of models are welcome. While the journal primarily focuses on theory-driven research, we also welcome experimental studies that validate and test theoretical conclusions.

《Frontiers in Computational Neuroscience》是一本顶尖的电子期刊，致力于推动大脑功能的理论建模，促进理论与实验神经科学之间的跨学科互动。尽管我们对大脑的惊人能力的理解仍然有限，但我们相信，只有通过深入的理论思考和不同学科及方法之间的相互促进合作，才能取得突破。因此，我们邀请对广泛主题的原创贡献，以展示这种合作的成果，或为未来的联盟提供启发。我们的目标是为神经系统的前沿理论研究提供一个互动论坛，并向更广泛的神经科学界传播最优秀的理论研究。从生物物理驱动的神经元和突触的逼真模拟，到推理和决策的高级抽象模型，各种风格和所有级别的模型都受到欢迎。虽然该期刊主要侧重于基于理论和驱动的研究，但我们也欢迎验证和测试理论结论的实验研究。

A Computational Model of the Cholinergic Modulation of CA1 Pyramidal Cell Activity

A model of CA1 pyramidal neuron that takes into consideration muscarinic receptor activation in response to changes in extracellular concentration of acetylcholine and its effects on cellular excitability and downstream intracellular calcium dynamics is developed.

Category	Quartile
医学	4
医学, 数学与计算生物学	3
医学, 神经科学	4

A Computational Model of the Cholinergic Modulation of CA1 Pyramidal Cell Activity

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