Blue Brain Project (BBP), École Polytechnique Fédérale de Lausanne (EPFL) Biotech Campus, Geneva, Switzerland.
Front Neural Circuits. 2018 Oct 9;12:77. doi: 10.3389/fncir.2018.00077. eCollection 2018.
Neuromodulators, such as acetylcholine (ACh), control information processing in neural microcircuits by regulating neuronal and synaptic physiology. Computational models and simulations enable predictions on the potential role of ACh in reconfiguring network activity. As a prelude into investigating how the cellular and synaptic effects of ACh collectively influence emergent network dynamics, we developed a data-driven framework incorporating phenomenological models of the physiology of cholinergic modulation of neocortical cells and synapses. The first-draft models were integrated into a biologically detailed tissue model of neocortical microcircuitry to investigate the effects of levels of ACh on diverse neuron types and synapses, and consequently on emergent network activity. Preliminary simulations from the framework, which was not tuned to reproduce any specific ACh-induced network effects, not only corroborate the long-standing notion that ACh desynchronizes spontaneous network activity, but also predict that a dose-dependent activation of ACh gives rise to a spectrum of neocortical network activity. We show that low levels of ACh, such as during non-rapid eye movement (nREM) sleep, drive microcircuit activity into slow oscillations and network synchrony, whereas high ACh concentrations, such as during wakefulness and REM sleep, govern fast oscillations and network asynchrony. In addition, spontaneous network activity modulated by ACh levels shape spike-time cross-correlations across distinct neuronal populations in strikingly different ways. These effects are likely due to the regulation of neurons and synapses caused by increasing levels of ACh, which enhances cellular excitability and decreases the efficacy of local synaptic transmission. We conclude by discussing future directions to refine the biological accuracy of the framework, which will extend its utility and foster the development of hypotheses to investigate the role of neuromodulators in neural information processing.
神经调质，如乙酰胆碱（ACh），通过调节神经元和突触生理学来控制神经微电路中的信息处理。计算模型和模拟使我们能够预测 ACh 在重新配置网络活动方面的潜在作用。作为研究 ACh 的细胞和突触效应如何共同影响新兴网络动力学的前奏，我们开发了一个数据驱动的框架，该框架结合了胆碱能调制新皮层细胞和突触生理学的现象学模型。初步模型被整合到新皮层微电路的详细生物学模型中，以研究 ACh 水平对不同神经元类型和突触的影响，以及对新兴网络活动的影响。该框架的初步模拟没有经过调整以再现任何特定的 ACh 诱导的网络效应，不仅证实了 ACh 使自发网络活动去同步的长期观点，而且还预测了 ACh 的剂量依赖性激活会导致新皮层网络活动的光谱。我们表明，低水平的 ACh，如在非快速眼动（nREM）睡眠期间，会使微电路活动进入缓慢振荡和网络同步，而高水平的 ACh，如在觉醒和 REM 睡眠期间，会控制快速振荡和网络异步。此外，ACh 水平调制的自发网络活动以截然不同的方式塑造不同神经元群体之间的尖峰时间交叉相关。这些效应可能是由于 ACh 水平的升高导致神经元和突触的调节，从而增强细胞兴奋性并降低局部突触传递的效率。最后，我们讨论了进一步提高框架生物学准确性的未来方向，这将扩展其效用，并促进发展假设以研究神经调质在神经信息处理中的作用。
