Li Qiang, Song Jiang-Ling, Li Si-Hui, Westover M Brandon, Zhang Rui
Medical Big Data Research Center, Northwest University, Xi'an, China.
Department of Neurology, Massachusetts General Hospital, Boston, MA, United States.
Front Comput Neurosci. 2020 Jan 23;13:100. doi: 10.3389/fncom.2019.00100. eCollection 2019.
It has been suggested that cholinergic neurons shape the oscillatory activity of the thalamocortical (TC) network in behavioral and electrophysiological experiments. However, theoretical modeling demonstrating how cholinergic neuromodulation of thalamocortical rhythms during non-rapid eye movement (NREM) sleep might occur has been lacking. In this paper, we first develop a novel computational model (TC-ACH) by incorporating a cholinergic neuron population (CH) into the classical thalamo-cortical circuitry, where connections between populations are modeled in accordance with existing knowledge. The neurotransmitter acetylcholine (ACH) released by neurons in CH, which is able to change the discharge activity of thalamocortical neurons, is the primary focus of our work. Simulation results with our TC-ACH model reveal that the cholinergic projection activity is a key factor in modulating oscillation patterns in three ways: (1) transitions between different patterns of thalamocortical oscillations are dramatically modulated through diverse projection pathways; (2) the model expresses a stable spindle oscillation state with certain parameter settings for the cholinergic projection from CH to thalamus, and more spindles appear when the strength of cholinergic input from CH to thalamocortical neurons increases; (3) the duration of oscillation patterns during NREM sleep including K-complexes, spindles, and slow oscillations is longer when cholinergic input from CH to thalamocortical neurons becomes stronger. Our modeling results provide insights into the mechanisms by which the sleep state is controlled, and provide a theoretical basis for future experimental and clinical studies.
在行为学和电生理学实验中，有人提出胆碱能神经元塑造了丘脑皮质（TC）网络的振荡活动。然而，一直缺乏理论模型来证明在非快速眼动（NREM）睡眠期间丘脑皮质节律的胆碱能神经调节是如何发生的。在本文中，我们首先通过将胆碱能神经元群体（CH）纳入经典的丘脑 - 皮质回路，开发了一种新型计算模型（TC - ACH），其中群体之间的连接是根据现有知识建模的。我们工作的主要重点是CH中神经元释放的神经递质乙酰胆碱（ACH），它能够改变丘脑皮质神经元的放电活动。我们的TC - ACH模型的模拟结果表明，胆碱能投射活动是通过三种方式调节振荡模式的关键因素：（1）通过不同的投射途径显著调节丘脑皮质振荡的不同模式之间的转换；（2）对于从CH到丘脑的胆碱能投射，模型在某些参数设置下表现出稳定的纺锤体振荡状态，并且当从CH到丘脑皮质神经元的胆碱能输入强度增加时，会出现更多的纺锤体；（3）当从CH到丘脑皮质神经元的胆碱能输入变强时，NREM睡眠期间包括K复合波、纺锤体和慢振荡在内的振荡模式持续时间更长。我们的建模结果为睡眠状态的控制机制提供了见解，并为未来的实验和临床研究提供了理论基础。
