DECREASED EFFECTIVENESS OF GABA-MEDIATED INHIBITION IN THE INFERIOR COLLICULUS OF THE GENETICALLY EPILEPSY-PRONE RAT
DECREASED EFFECTIVENESS OF GABA-MEDIATED INHIBITION IN THE INFERIOR COLLICULUS OF THE GENETICALLY EPILEPSY-PRONE RAT
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DOI：
10.1016/0014-4886(86)90154-8
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发表时间：
1986-07-01
影响因子：
5.3
通讯作者：
CASPARY, DM
中科院分区：
文献类型：
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作者：
FAINGOLD, CL;GEHLBACH, G;CASPARY, DM
下丘(IC)是遗传性癫痫易感大鼠(GEPR)诱发听源性癫痫发作的关键部位。在该品系的下丘神经元中观察到的异常反应特性包括高发生率的起始-偏移反应，这可能是后放电的一种形式。这些反应异常可能涉及大脑该区域神经递质活动的改变。GABA在内源性声音诱导的下丘抑制中是一种递质。本文研究了癫痫大鼠和正常大鼠下丘神经元的内源性抑制作用和影响GABA受体的药物的作用。抑制癫痫易感大鼠神经元放电所需的GABA离子导入剂量(电流)明显大于正常大鼠神经元所需的剂量(电流)。与正常大鼠相比，癫痫易感大鼠下丘神经元的一种内源性(双耳)抑制也显著减少，这被认为是由GABA介导的。一种苯二氮卓类药物(氟西潘)在包括下丘在内的许多大脑部位增强GABA的作用，但在癫痫易感大鼠的相同神经元上应用离子电泳法时，效果明显低于正常水平。GABAA拮抗剂荷包牡丹碱阻断GABA对下丘神经元的作用，经常在以前没有表现出这种模式的神经元中诱导起始-抵消反应。这些结果表明，在遗传性癫痫易感大鼠中，GABA介导的抑制作用的减少可能导致下丘神经元后放电的增加，这可能是这种遗传性癫痫的听源性癫痫发作的一个重要机制。
The inferior colliculus (IC) is a critical site for induction of audiogenic seizures in the genetically epilepsy-prone rat (GEPR). Abnormal response properties observed in inferior colliculus neurons of that strain include a high incidence of onset-offset responses which may be a form of afterdischarge. These response abnormalities may involve altered actions of neurotransmitters in that region of the brain. GABA is implicated as a transmitter in endogenous sound-induced inhibition in the inferior colliculus. Endogenous inhibition and the actions of agents that affect GABA receptors were examined in inferior colliculus neurons in epileptic and normal rats. The iontophoretic dose (current) of GABA required to suppress neuronal firing in the epilepsy-prone rat was significantly greater than that required in neurons of the normal rat. A form of endogenous (binaural) inhibition in inferior colliculus neurons, which is proposed to be GABA-mediated, was also significantly reduced in the epilepsy-prone rat as compared with the normal rat. A benzodiazepine (flurazepam) which enhances the action of GABA in many brain sites including the inferior colliculus was significantly less effective than normal when applied iontophoretically onto the same neurons of the epilepsy-prone rat. The GABAA antagonist, bicuculline, which blocks the effect of GABA on inferior colliculus neurons, frequently induced the onset-offset response in neurons not previously exhibiting this pattern. These findings suggest that the reduction of GABA-mediated inhibition in the genetically epilepsy-prone rat may result in the increased icidence of afterdischarges in neurons of the inferior colliculus and may serve as an important mechanism of epileptogenesis in audiogenic seizures in this genetic form of epilepsy.