Swann J W, Smith K L, Brady R J
Cain Foundation Laboratories, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
J Neurosci. 1993 Nov;13(11):4680-9. doi: 10.1523/JNEUROSCI.13-11-04680.1993.
Repetitive synchronized neuronal discharging that lasts for seconds and even minutes in in vitro brain slice preparations are important new models in experimental epilepsy. In hippocampal slices from 1-2-week-old rats, individual CA3 pyramidal cells undergo a sustained depolarization during such electrographic seizures, induced by GABAA receptor antagonists. In experiments reported here these events were produced in small isolated segments of the CA3 subfield, measuring only 400-500 microns along the cell body layer. In such minisclices local application of either kynurenic acid or 6-cyano-7-nitroquinoxaline-2-3-dione (CNQX) to the proximal basilar dendrites abolished the synchronized discharges of electrographic seizures. Interictal spikes appeared unaffected by this treatment. Application of these excitatory amino acid receptor antagonists to distal basilar dendrites or apical dendrites was ineffective. In "larger" minislices, measuring 700-1000 microns along the cell body layer, application of kynurenic acid, CNQX, or TTX to the proximal basilar dendrites did not abolish electrographic seizures but instead selectively suppressed the intracellularly recorded sustained depolarization and the coincident slow negative field potential recorded in proximal basilar dendrites. Results of several experiments suggest that electrographic seizures recorded under these conditions were produced by a remote network of "generator cells." Since the remote neurons were unaffected by local application of the drugs, it seemed likely that they continued to undergo a sustained depolarization. Simultaneous blockade of basilar dendritic synapses in the "generator" population abolished electrographic seizures throughout these larger minislices. These results suggest that the sustained depolarization plays a central role in seizure generation and that it does not have to be generated in every neuron, only in a critical number of "generator cells" for a seizure to occur. Taken together, results presented here suggest that the sustained depolarization of electrographic seizures is a separate physiological process from the more rapid repetitive depolarizations of the seizure discharges and is required if electrographic seizures are to occur. This slow depolarization appears to be synaptically mediated and generated exclusively in proximal basilar dendrites. Therefore, in addition to the excitatory synaptic potentials involved in paroxysmal depolarization shift generation, a second form of recurrent excitation may exist in immature hippocampus. Not only is this physiological process critical for the genesis of seizures, but it also appears to be highly partitioned within the hippocampal laminae.
在体外脑片制备中持续数秒甚至数分钟的重复性同步神经元放电是实验性癫痫的重要新模型。在1至2周龄大鼠的海马切片中，单个CA3锥体细胞在由GABAA受体拮抗剂诱导的这种脑电图癫痫发作期间经历持续去极化。在本文报道的实验中，这些事件发生在CA3亚区的小分离片段中，沿着细胞体层仅测量400 - 500微米。在这种微型切片中，向近端基底树突局部应用犬尿喹啉酸或6 - 氰基 - 7 - 硝基喹喔啉 - 2,3 - 二酮（CNQX）可消除脑电图癫痫发作的同步放电。发作间期棘波似乎不受此治疗影响。将这些兴奋性氨基酸受体拮抗剂应用于远端基底树突或顶端树突无效。在沿着细胞体层测量为700 - 1000微米的“较大”微型切片中，向近端基底树突应用犬尿喹啉酸、CNQX或TTX并没有消除脑电图癫痫发作，而是选择性地抑制了细胞内记录的持续去极化以及在近端基底树突中记录的同步慢负场电位。几个实验的结果表明，在这些条件下记录的脑电图癫痫发作是由“发生器细胞”的远程网络产生的。由于远程神经元不受药物局部应用的影响，它们似乎继续经历持续去极化。同时阻断“发生器”群体中的基底树突突触可消除整个这些较大微型切片中的脑电图癫痫发作。这些结果表明，持续去极化在癫痫发作产生中起核心作用，并且它不必在每个神经元中产生，仅在一定数量的关键“发生器细胞”中产生才能发生癫痫发作。综上所述，本文给出的结果表明，脑电图癫痫发作的持续去极化是一个与癫痫放电更快速的重复性去极化不同的生理过程，并且如果要发生脑电图癫痫发作则是必需的。这种缓慢去极化似乎是由突触介导的，并且仅在近端基底树突中产生。因此，除了参与阵发性去极化移位产生的兴奋性突触电位外，在未成熟海马中可能存在第二种形式的反复性兴奋。这种生理过程不仅对癫痫发作的发生至关重要，而且似乎在海马层内高度分隔。
