Telfeian A E, Connors B W
Department of Neuroscience, Brown University, Providence, Rhode Island 02912, USA.
Epilepsia. 1998 Jul;39(7):700-8. doi: 10.1111/j.1528-1157.1998.tb01154.x.
Epileptiform discharges that resemble interictal spikes can be generated by slices of neocortex treated with antagonists of gamma-aminobutyric acid A (GABA(A)) receptors. These discharges can propagate horizontally for long distances. We tested the hypothesis that propagation occurs through preferred horizontal pathways that lie in a particular cortical layer.
Slices were prepared from the primary somatosensory cortex of rats, maintained in vitro, and bathed with the GABA(A) receptor antagonist picrotoxin. Electrical stimuli were used to evoke single all-or-none paroxysmal field potentials (PFP) that were recorded with pairs or arrays of field potential electrodes.
To test which laminae are necessary for propagation, vertical cuts were made to force the PFP to spread horizontally through particular layers. If slices were bathed in a high dose of picrotoxin (35 microM), a bridge of cortex 350 microm thick placed at any lamina was sufficient to support PFP propagation. However, in low picrotoxin doses (2.5 microM), similarly sized bridges had to include tissue from layers 4/5 or 5/6 to support propagation. When slices were cut horizontally (i.e., parallel to the pia) in strips. either upper-, middle-, or lower-layer strips were sufficient to support PFP propagation if the picrotoxin concentration was high; however, in low picrotoxin doses, only horizontal strips that included layer 5 could support propagation. Finally, in intact picrotoxin-treated slices, focal applications of GABA were systematically applied to different laminae as the PFP propagated past; GABA was most effective at blocking or delaying propagation when it was applied to layer 5b.
We conclude that epileptiform propagation can occur through a variety of horizontal pathways when cortical inhibition is strongly impaired. However, when inhibition is reduced only moderately, axonal pathways in layer 5 are critical for seizure spread.
用γ-氨基丁酸A（GABA(A)）受体拮抗剂处理的新皮层切片可产生类似于发作间期棘波的癫痫样放电。这些放电可沿水平方向远距离传播。我们检验了这样一种假说，即传播是通过位于特定皮层层的优先水平通路发生的。
从大鼠的初级体感皮层制备切片，在体外维持，并浸浴于GABA(A)受体拮抗剂印防己毒素中。使用电刺激诱发单个全或无阵发性场电位（PFP），用场电位电极对或电极阵列进行记录。
为了测试哪些层对于传播是必需的，进行垂直切割以使PFP水平穿过特定层传播。如果切片浸浴于高剂量的印防己毒素（35微摩尔）中，置于任何层的350微米厚的皮层桥足以支持PFP传播。然而，在低剂量印防己毒素（2.5微摩尔）时，同样大小的桥必须包含来自第4/5层或5/6层的组织才能支持传播。当将切片水平切成条带（即平行于软脑膜）时，如果印防己毒素浓度高，上层、中层或下层条带都足以支持PFP传播；然而，在低剂量印防己毒素时，只有包含第5层的水平条带才能支持传播。最后，在完整的经印防己毒素处理的切片中，当PFP传播过去时，将GABA局部应用于不同层；当将GABA应用于第5b层时，对阻断或延迟传播最有效。
我们得出结论，当皮层抑制严重受损时，癫痫样传播可通过多种水平通路发生。然而，当抑制仅适度降低时，第5层的轴突通路对于癫痫发作传播至关重要。
