Anesthesiology. 2021 Feb 1;134(2):219-233. doi: 10.1097/ALN.0000000000003653.
The general anesthetic propofol induces frontal alpha rhythm in the cerebral cortex at a dose sufficient to induce loss of consciousness. The authors hypothesized that propofol-induced facilitation of unitary inhibitory postsynaptic currents would result in firing synchrony among postsynaptic pyramidal neurons that receive inhibition from the same presynaptic inhibitory fast-spiking neurons.
Multiple whole cell patch clamp recordings were performed from one fast-spiking neuron and two or three pyramidal neurons with at least two inhibitory connections in rat insular cortical slices. The authors examined how inhibitory inputs from a presynaptic fast-spiking neuron modulate the timing of spontaneous repetitive spike firing among pyramidal neurons before and during 10 μM propofol application.
Responding to activation of a fast-spiking neuron with 150-ms intervals, pyramidal cell pairs that received common inhibitory inputs from the presynaptic fast-spiking neuron showed propofol-dependent decreases in average distance from the line of identity, which evaluates the coefficient of variation in spike timing among pyramidal neurons: average distance from the line of identity just after the first activation of fast-spiking neuron was 29.2 ± 24.1 (mean ± SD, absolute value) in control and 19.7 ± 19.2 during propofol application (P < 0.001). Propofol did not change average distance from the line of identity without activating fast-spiking neurons and in pyramidal neuron pairs without common inhibitory inputs from presynaptic fast-spiking neurons. The synchronization index, which reflects the degree of spike synchronization among pyramidal neurons, was increased by propofol from 1.4 ± 0.5 to 2.3 ± 1.5 (absolute value, P = 0.004) and from 1.5 ± 0.5 to 2.2 ± 1.0 (P = 0.030) when a presynaptic fast-spiking neuron was activated at 6.7 and 10 Hz, respectively, but not at 1, 4, and 13.3 Hz.
These results suggest that propofol facilitates pyramidal neuron firing synchrony by enhancing inhibitory inputs from fast-spiking neurons. This synchrony of pyramidal neurons may contribute to the alpha rhythm associated with propofol-induced loss of consciousness.
全身麻醉药物异丙酚可诱导大脑皮层的额阿尔法节律，其剂量足以诱导意识丧失。作者假设，异丙酚诱导的单位抑制性突触后电流易化作用会导致从同一突触前抑制性快速放电神经元接收抑制的突触后锥体细胞之间的放电同步。
在大鼠岛叶皮质切片中，对一个快速放电神经元和两个或三个具有至少两个抑制性连接的锥体细胞进行了多次全细胞膜片钳记录。作者检查了在 10μM 异丙酚应用前后，来自突触前快速放电神经元的抑制性输入如何调节锥体细胞自发重复放电的时间。
在以 150ms 间隔激活快速放电神经元时，从突触前快速放电神经元接收共同抑制性输入的两个锥体细胞对表现出与异丙酚依赖性降低的平均距离，该距离评估了锥体细胞间的放电时间变异性的系数：在对照中，在快速放电神经元首次激活后的平均距离为 29.2±24.1（平均值±标准差，绝对值），而在异丙酚应用期间为 19.7±19.2（P<0.001）。如果不激活快速放电神经元且没有来自突触前快速放电神经元的共同抑制性输入，则异丙酚不会改变无距离线的平均距离。在没有来自突触前快速放电神经元的共同抑制性输入的锥体细胞对中，同步指数（反映锥体细胞间的放电同步程度）由异丙酚从 1.4±0.5 增加到 2.3±1.5（绝对值，P=0.004）和从 1.5±0.5 增加到 2.2±1.0（P=0.030），当以 6.7 和 10Hz 分别激活突触前快速放电神经元时，但在 1、4 和 13.3Hz 时没有。
这些结果表明，异丙酚通过增强来自快速放电神经元的抑制性输入来促进锥体细胞的放电同步。这种锥体细胞的同步可能有助于与异丙酚诱导的意识丧失相关的阿尔法节律。
