Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
ICREA, Passeig Lluís Companys, Barcelona, Spain.
PLoS Comput Biol. 2023 Jul 5;19(7):e1011246. doi: 10.1371/journal.pcbi.1011246. eCollection 2023 Jul.
The slow oscillation is a synchronized network activity expressed by the cortical network in slow wave sleep and under anesthesia. Waking up requires a transition from this synchronized brain state to a desynchronized one. Cholinergic innervation is critical for the transition from slow-wave-sleep to wakefulness, and muscarinic action is largely exerted through the muscarinic-sensitive potassium current (M-current) block. We investigated the dynamical impact of blocking the M-current on slow oscillations, both in cortical slices and in a cortical network computational model. Blocking M-current resulted in an elongation of Up states (by four times) and in a significant firing rate increase, reflecting an increased network excitability, albeit no epileptiform discharges occurred. These effects were replicated in a biophysical cortical model, where a parametric reduction of the M-current resulted in a progressive elongation of Up states and firing rate. All neurons, and not only those modeled with M-current, increased their firing rates due to network recurrency. Further increases in excitability induced even longer Up states, approaching the microarousals described in the transition towards wakefulness. Our results bridge an ionic current with network modulation, providing a mechanistic insight into network dynamics of awakening.
慢波振荡是皮质网络在慢波睡眠和麻醉状态下表达的同步网络活动。唤醒需要从这种同步的大脑状态过渡到去同步的状态。胆碱能神经支配对于从慢波睡眠到觉醒的过渡至关重要，而毒蕈碱作用主要通过毒蕈碱敏感钾电流（M 电流）阻断来发挥。我们研究了阻断 M 电流对皮质切片和皮质网络计算模型中慢波振荡的动力学影响。阻断 M 电流导致 Up 状态延长（延长四倍）和显著的放电率增加，反映出网络兴奋性增加，尽管没有发生癫痫样放电。这些效应在生物物理皮质模型中得到了复制，其中 M 电流的参数减少导致 Up 状态和放电率的逐渐延长。由于网络递归，所有神经元（不仅仅是那些用 M 电流建模的神经元）都增加了它们的放电率。兴奋性的进一步增加甚至导致更长的 Up 状态，接近向觉醒过渡过程中描述的微觉醒。我们的结果将离子电流与网络调制联系起来，为唤醒的网络动力学提供了一种机制上的见解。
