Isomura Yoshikazu, Fujiwara-Tsukamoto Yoko, Takada Masahiko
Department of System Neuroscience, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan.
J Neurophysiol. 2003 Oct;90(4):2746-51. doi: 10.1152/jn.00057.2003.
Previous investigations have suggested that GABA may act actively as an excitatory mediator in the generation of seizure-like (ictal) or interictal epileptiform activity in several experimental models of temporal lobe epilepsy. However, it remains to be known whether or not such GABAergic excitation may participate in seizure propagation into neighboring cortical regions. In our in vitro study using mature rat hippocampal slices, we examined the cellular mechanism underlying synchronous propagation of seizure-like afterdischarge in the CA1 region, which is driven by depolarizing GABAergic transmission, into the adjacent subiculum region. Tetanically induced seizure-like afterdischarge was always preceded by a GABAergic, slow posttetanic depolarization in the pyramidal cells of the original seizure-generating region. In contrast, the slow posttetanic depolarization was no longer observed in the subicular pyramidal cells when the afterdischarge was induced in the CA1 region. Surgical cutting of axonal pathways through the stratum oriens and the alveus between the CA1 and the subiculum region abolished the CA1-generated afterdischarge in the subicular pyramidal cells. Intracellular loading of fluoride ions, a GABAA receptor blocker, into single subicular pyramidal cells had no inhibitory effect on the CA1-generated afterdischarge in the pyramidal cells. Furthermore, the CA1-generated afterdischarge in the subicular pyramidal cells was largely depressed by local application of glutamate receptor antagonists to the subiculum region during afterdischarge generation. The present results indicate that the excitatory GABAergic generation of seizure-like activity seems to be restricted to epileptogenic foci of origin in the seizure-like epilepsy model in vitro.
先前的研究表明，在几种颞叶癫痫实验模型中，γ-氨基丁酸（GABA）可能作为一种兴奋性介质，积极参与癫痫样（发作期）或发作间期癫痫样活动的产生。然而，这种GABA能兴奋是否参与癫痫发作向邻近皮质区域的传播仍有待确定。在我们使用成年大鼠海马切片的体外研究中，我们研究了在CA1区由去极化GABA能传递驱动的癫痫样后放电同步传播到相邻海马下托区的细胞机制。强直刺激诱发的癫痫样后放电总是先于原始癫痫发作区锥体细胞中GABA能的、强直后缓慢去极化。相比之下，当在CA1区诱发后放电时，在海马下托锥体细胞中不再观察到强直后缓慢去极化。通过切断CA1区和海马下托区之间的海马床层和海马槽的轴突通路，消除了海马下托锥体细胞中由CA1区产生的后放电。将GABAA受体阻断剂氟离子细胞内注入单个海马下托锥体细胞，对CA1区产生的锥体细胞后放电没有抑制作用。此外，在海马下托区局部应用谷氨酸受体拮抗剂，在很大程度上抑制了海马下托锥体细胞中由CA1区产生的后放电。目前的结果表明，在体外癫痫样癫痫模型中，癫痫样活动的兴奋性GABA能产生似乎局限于癫痫起源灶。
