HORIZONTAL SPREAD OF SYNCHRONIZED ACTIVITY IN NEOCORTEX AND ITS CONTROL BY GABA-MEDIATED INHIBITION
HORIZONTAL SPREAD OF SYNCHRONIZED ACTIVITY IN NEOCORTEX AND ITS CONTROL BY GABA-MEDIATED INHIBITION
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DOI：
10.1152/jn.1989.61.4.747
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发表时间：
1989-04-01
影响因子：
2.5
通讯作者：
CONNORS, BW
中科院分区：
文献类型：
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作者：
CHAGNACAMITAI, Y;CONNORS, BW
1.抑制GABAA受体介导的抑制会破坏新皮层的神经活动，并可导致模仿部分性癫痫的同步放电。我们已经研究了GABAA介导的抑制在控制皮层活动的同步和水平（切向）传播中的作用。2.大鼠SmI切片保持在体外，并在VI层局部刺激，同时记录与细胞外电极的水平阵列。通过向浴液中加入低浓度的GABAA拮抗剂荷包牡丹碱或荷包牡丹碱甲碘化物，抑制作用略有抑制。在控制条件下，神经活动被严格限制在一个垂直带的皮层。在预期抑制GABAA功能不超过10- 20%的拮抗剂浓度（小于或等于0.5 μ M）存在下，活性的水平扩散扩大约两倍。3.在0.4和1.0 μ M之间的拮抗剂浓度，诱发癫痫样活动出现。这些阈值剂量癫痫样事件表现出很大的变化，在大小和持续时间（即使在同一个记录网站），非常可变的距离水平传播，传播失败的特定网站，传播方向的逆转，和方向的不对称性，在他们的传播概率。这与先前在高荷包牡丹碱浓度（大于或等于10 μ M）下观察到的活性形成对比（参考文献9）：大的定型事件可靠地传播，没有衰减或反射。4.细胞内的记录，从锥体神经元层II/III中的存在下，小于或等于1 μ M荷包牡丹碱。抑制性突触后电位（IPSPs）观察到在两个主要的诱发反应和传播癫痫样事件，往往是可比的大小和持续时间在未经处理的皮质。癫痫样场电位与单个细胞的突触活动密切相关，但场电位的形式不同，诱发电位的类型也不同。大幅度癫痫样事件与上层神经元的压倒性抑制相一致。5.我们的结论是：1）正常皮层活动的水平传播受到GABAA介导的IPSPs的强烈限制，2）抑制功效的相对较小的降低导致兴奋传播的大幅增加，3）即使在存在强大的皮层抑制的情况下，同步癫痫样活动的启动和传播也可以发生，（4）癫痫样活动的特征受抑制作用的影响。
1. Suppression of GABAA receptor-mediated inhibition disrupts the neural activity of neocortex and can lead to synchronized discharges that mimic those of partial epilepsy. We have studied the role of GABAA-mediated inhibition in controlling the synchronization and horizontal (tangential) spread of cortical activity. 2. Slices of rat SmI were maintained in vitro and focally stimulated in layer VI while recording with a horizontal array of extracellular electrodes. Inhibition was slightly suppressed by adding low concentrations of the GABAA antagonists bicuculline or bicuculline methiodide to the bathing medium. Under control conditions neural activity was narrowly confined to a vertical strip of cortex. The horizontal spread of activity expanded about twofold in the presence of antagonist concentrations (less than or equal to 0.5 microM) that were expected to suppress GABAA function by no more than 10-20%. 3. At antagonist concentrations between 0.4 and 1.0 microM, evoked epileptiform activity appeared. These threshold-dose epileptiform events showed wide variations in size and duration (even at the same recording site), very variable distances of horizontal propagation, specific sites of propagation failure, reversals of propagation direction, and directional asymmetries in their probability of propagation. This contrasts with activity observed previously (Ref. 9) in high bicuculline concentrations (greater than or equal to 10 microM): large, stereotyped events that propagate reliably without decrement or reflection. 4. Intracellular recordings were obtained from pyramidal neurons in layers II/III in the presence of less than or equal to 1 microM bicuculline. Inhibitory postsynaptic potentials (IPSPs) were observed during both primary evoked responses and propagating epileptiform events and were often comparable in size and duration to those in untreated cortex. Epileptiform field potentials were always correlated with synaptic activity in single cells, but the pattern and type of PSPs varied with the form of the field potentials. Large amplitude epileptiform events coincided with an overwhelming inhibition of upper layer neurons. 5. We conclude that 1) the horizontal spread of normal cortical activity is strongly constrained by GABAA-mediated IPSPs, 2) a relatively small reduction in the efficacy of inhibition leads to a large increase in the spread of excitation, 3) initiation and propagation of synchronized epileptiform activity can occur even in the presence of robust cortical inhibition, and 4) the character of epileptiform activity is strongly affected by the influences of inhibition.