Department of Anesthesiology, Weill Cornell Medical College, New York, New York 10021, USA.
Anesthesiology. 2012 Oct;117(4):780-90. doi: 10.1097/ALN.0b013e318269ba6d.
The understanding of how general anesthetics act on individual cells and on global brain function has increased significantly during the last decade. What remains poorly understood is how anesthetics act at intermediate scales. Several major theories emphasize the importance of neuronal groups, sets of strongly connected neurons that fire in a time-locked fashion, in all aspects of brain function, particularly as a necessary substrate of consciousness. The authors have undertaken computer modeling to determine how ã-aminobutyric acid receptor type A (GABAA) receptor potentiating agents such as propofol may influence the dynamics of neuronal group formation and ongoing activity.
A computer model of a cortical network with connections modified by synaptic plasticity was examined. At baseline, the model spontaneously formed neuronal groups. Direct effects of GABAA receptor potentiation and indirect effects on input drive were then examined to study their effects on this process.
Potentiation of GABAA inhibition and input drive reduction reduced the firing frequency of inhibitory and excitatory neurons in a dose-dependent manner. The diminution in spiking rates led to dramatic reductions in the firing frequency of neuronal groups. Simulated electroencephalographic output from the model at baseline exhibits gamma and theta rhythmicity. The direct and indirect GABAA effects reduce the amplitude of these underlying rhythms and modestly slow the gamma rhythm.
GABAA facilitation both directly and indirectly inhibits the ability of neurons to form groups spontaneously. A lack of group formation is consistent with some theories of anesthetic-induced loss of memory formation and consciousness.
在过去的十年中，人们对全身麻醉剂如何作用于单个细胞和大脑整体功能的理解有了显著提高。但人们对麻醉剂在中间尺度上的作用仍知之甚少。几个主要理论强调了神经元群的重要性，即一组以时间锁定方式发射的强连接神经元，在大脑功能的各个方面，特别是作为意识的必要基础方面都具有重要意义。作者已经进行了计算机建模，以确定 GABA 受体 A 型（GABAA）受体增强剂（如丙泊酚）如何影响神经元群形成和持续活动的动力学。
检查了一个具有突触可塑性连接的皮质网络的计算机模型。在基线状态下，该模型会自发形成神经元群。然后研究了 GABAA 受体增强和对输入驱动的间接影响的直接作用，以研究它们对这一过程的影响。
GABAA 抑制的增强和输入驱动的减少以剂量依赖的方式降低了抑制性和兴奋性神经元的放电频率。尖峰率的降低导致神经元群的放电频率显著降低。模型的基线模拟脑电图输出表现出伽马和θ节律性。直接和间接的 GABAA 效应降低了这些潜在节律的幅度，并适度减缓了伽马节律。
GABAA 促进作用直接和间接地抑制了神经元自发形成群组的能力。缺乏群组形成与一些关于麻醉诱导的记忆形成和意识丧失的理论是一致的。
