Seizures induce simultaneous GABAergic and glutamatergic transmission in the dentate Gyrus-CA3 system
Seizures induce simultaneous GABAergic and glutamatergic transmission in the dentate Gyrus-CA3 system
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DOI：
10.1152/jn.2000.84.6.3088
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发表时间：
2000-12-01
影响因子：
2.5
通讯作者：
Gutiérrez, R
中科院分区：
文献类型：
--
作者：
Gutiérrez, R
谷氨酸受体拮抗剂（GluRAs）可阻断海马CA 3区锥体细胞（PC）对齿状回（DG）刺激的单突触和多突触反应。然而，点燃癫痫发作后，GluRAs阻断单突触兴奋性突触后电位（EPSP）和分离单突触抑制性突触后电位（IPSP），表明苔藓纤维释放GABA。然而，点燃癫痫诱导神经元发芽，这可能是这种快速抑制反应的基础。为了探讨这种可能性，PC DG刺激的突触反应进行了分析点燃癫痫大鼠，癫痫发作和无癫痫发作，并在非癫痫大鼠，后立即一个单一的戊四氮（PTZ）诱导的癫痫发作，其中发芽是不可能发生。兴奋性和抑制性突触反应的PC DG刺激被阻断GluRAs在控制细胞和点燃nonseizing大鼠的细胞，证实抑制电位是双突触介导的。然而，点燃癫痫大鼠和非癫痫大鼠在单次PTZ诱导的癫痫发作后，可以诱发快速IPSP。再点燃未发作的癫痫大鼠也可诱发同样的反应。该IPSP具有与对照EPSP平行的起始潜伏期，并且在低Ca 2+介质或氟烷灌注下不改变。此外，它被L（+）-2-氨基-4-膦酰基丁酸（L-AP 4）可逆地抑制，已知L-AP 4抑制苔藓纤维的递质释放。这些结果表明，癫痫发作，而不是由于潜在的癫痫状态的突触重排，诱导DG-CA 3系统中出现快速抑制，并表明苔藓纤维的这种塑性变化的基础。
Monosynaptic and polysynaptic responses of CA3 pyramidal cells (PC) to stimulation of the dentate gyrus (DG) are normally blocked by glutamate receptor antagonists (GluRAs). However, after kindled seizures, GluRAs block the monosynaptic excitatory postsynaptic potential (EPSP) and isolate a monosynaptic inhibitory postsynaptic potential (IPSP), suggesting that mossy fibers release GABA. However, kindling epilepsy induces neuronal sprouting, which can underlie this fast inhibitory response. To explore this possibility, the synaptic responses of PC to DG stimulation were analyzed in kindled epileptic rats, with and without seizures, and in nonepileptic rats, immediately after a single pentylenetetrazol (PTZ)-induced seizure, in which sprouting is unlikely to have occurred. Excitatory and inhibitory synaptic responses of PC to DG stimulation were blocked by GluRAs in control cells and in cells from kindled nonseizing rats, confirming that inhibitory potentials are disynaptically mediated. However, a fast IPSP could be evoked in kindled epileptic rats and in nonepileptic rats after a single PTZ-induced seizure. The same response was induced after rekindling the epileptic nonseizing rats. This IPSP has an onset latency that parallels that of the control EPSP and is not altered under low Ca2+ medium or halothane perfusion. In addition, it was reversibly depressed by L(+)-2- amino-4-phosphonobutyric acid (L-AP4), which is known to inhibit transmitter release from mossy fibers. These results demonstrate that seizures, and not the synaptic rearrangement due to an underlying epileptic state, induce the emergence of fast inhibition in the DG-CA3 system, and suggest that the mossy fibers underlie this plastic change.