From the Department of Anesthesiology, Weill Cornell Medical College, New York, New York (K.P.S) the Laboratory of Biological Modeling, The Rockefeller University, New York, New York (K.P.S, G.N.R.) the Department of Surgery, Flinders University, Adelaide, Australia (K.P.S).
Anesthesiology. 2018 Jul;129(1):106-117. doi: 10.1097/ALN.0000000000002230.
Propofol produces memory impairment at concentrations well below those abolishing consciousness. Episodic memory, mediated by the hippocampus, is most sensitive. Two potentially overlapping scenarios may explain how γ-aminobutyric acid receptor type A (GABAA) potentiation by propofol disrupts episodic memory-the first mediated by shifting the balance from excitation to inhibition while the second involves disruption of rhythmic oscillations. We use a hippocampal network model to explore these scenarios. The basis for these experiments is the proposal that the brain represents memories as groups of anatomically dispersed strongly connected neurons.
A neuronal network with connections modified by synaptic plasticity was exposed to patterned stimuli, after which spiking output demonstrated evidence of stimulus-related neuronal group development analogous to memory formation. The effect of GABAA potentiation on this memory model was studied in 100 unique networks.
GABAA potentiation consistent with moderate propofol effects reduced neuronal group size formed in response to a patterned stimulus by around 70%. Concurrently, accuracy of a Bayesian classifier in identifying learned patterns in the network output was reduced. Greater potentiation led to near total failure of group formation. Theta rhythm variations had no effect on group size or classifier accuracy.
Memory formation is widely thought to depend on changes in neuronal connection strengths during learning that enable neuronal groups to respond with greater facility to familiar stimuli. This experiment suggests the ability to form such groups is sensitive to alteration in the balance between excitation and inhibition such as that resulting from administration of a γ-aminobutyric acid-mediated anesthetic agent.
丙泊酚在低于意识消除浓度的浓度下即可产生记忆损伤。由海马体介导的情景记忆最为敏感。两种可能重叠的情况可以解释丙泊酚增强γ-氨基丁酸 A 型受体（GABAA）如何破坏情景记忆——第一种是通过将兴奋与抑制之间的平衡转移来介导，第二种是涉及到节律性振荡的破坏。我们使用海马体网络模型来探索这些情况。这些实验的基础是提出大脑将记忆表示为一组解剖上分散的强连接神经元。
一个连接通过突触可塑性改变的神经元网络被暴露于模式化刺激下，之后，尖峰输出表现出类似于记忆形成的与刺激相关的神经元组发展的证据。在 100 个独特的网络中研究了 GABAA 增强对这个记忆模型的影响。
与中等丙泊酚效应一致的 GABAA 增强将对模式化刺激的反应中形成的神经元组的大小减少了约 70%。同时，贝叶斯分类器在识别网络输出中学习模式的准确性也降低了。更大的增强导致组形成几乎完全失败。θ节律变化对组大小或分类器准确性没有影响。
记忆形成被广泛认为依赖于学习过程中神经元连接强度的变化，这些变化使神经元组能够更轻松地对熟悉的刺激做出反应。这个实验表明，形成这种组的能力对兴奋与抑制之间平衡的改变很敏感，例如给予γ-氨基丁酸介导的麻醉剂会导致这种平衡改变。
