LOSS OF SYNAPTIC INHIBITION DURING REPETITIVE STIMULATION IN GENETICALLY EPILEPSY-PRONE RATS (GEPR)
LOSS OF SYNAPTIC INHIBITION DURING REPETITIVE STIMULATION IN GENETICALLY EPILEPSY-PRONE RATS (GEPR)
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DOI：
10.1016/0920-1211(94)90002-7
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发表时间：
1994-06-01
影响因子：
2.2
通讯作者：
FAINGOLD, CL
中科院分区：
文献类型：
--
作者：
EVANS, MS;VIOLAMCCABE, KE;FAINGOLD, CL
遗传性癫痫易感大鼠（GEPR）是一种全身性运动性癫痫发作的动物模型。GEPR中癫痫发作倾向的根本原因尚未完全确定。脑干听觉系统对于GEPR中的听源性癫痫发作至关重要，并且在这些区域中已经观察到神经生理学异常，但最近的证据表明非听觉脑区也可能异常。这可能是各种非听源性癫痫发作的GEPR阈值降低的原因。由于海马Schaffer侧支/CA 1突触的正常反应是相对较好的理解，我们研究了单一的和重复的突触反应在海马切片的GEPR在体外。我们的假设是，兴奋性或抑制性突触传递的改变可能有助于GEPR非听源性癫痫倾向。我们记录了细胞外EPSP，群体尖峰，和传入齐射在海马CA 1区，并比较GEPR反应的Sprague-Dawley（SD）大鼠，从该株GEPR的衍生。单突触刺激的GEPR反应没有显着不同的SD。一对紧密间隔的EPSP或群体尖峰的第二个在GEPR和SD（成对脉冲易化）中都较大，但群体尖峰易化的幅度在GEPR中显著增加。短列车的四个刺激引起抑制的人口尖峰放电在SD，效果大大减少GEPR。当SD脑片用GABA（A）受体拮抗剂荷包牡丹碱处理时，在一连串刺激期间观察到增强的成对脉冲易化和抑制丧失，与GEPR中观察到的模式相似。先前在GEPR的另一个脑区（下丘）的研究显示神经元抑制丧失，药理学研究与GABA介导的抑制减少一致。目前的研究表明，异常减少的神经元抑制也存在于GEPR前脑，并导致夸张的倾向，消防动作电位，这可能是一个重要因素GEPR癫痫易感性。
Genetically epilepsy-prone rats (GEPR) are an animal model of generalized motor seizures. The underlying causes of the predisposition to seizures in GEPR have not been fully determined. The brainstem auditory system is critical for audiogenic seizures in GEPR, and neurophysiological abnormalities have been observed in these areas, but recent evidence suggests that non-auditory brain areas may also be abnormal. This may account for the lowered threshold in GEPR for various non-audiogenic seizures. Because the normal responses of the hippocampal Schaffer collateral/CA1 synapse are relatively well understood, we studied single and repetitive synaptic responses in hippocampal slices of GEPR in vitro. Our hypothesis was that altered excitatory or inhibitory synaptic transmission may contribute to GEPR non-audiogenic seizure predisposition. We recorded extracellular EPSPs, population spikes, and afferent volleys in hippocampal area CA1, and compared GEPR responses to those of Sprague-Dawley (SD) rats, the strain from which GEPR were derived. GEPR responses to single synaptic stimuli were not significantly different from SD. The second of a pair of closely spaced EPSPs or population spikes was larger in both GEPR and SD (paired pulse facilitation), but the magnitude of population spike facilitation was significantly increased in GEPR. Short trains of four stimuli caused inhibition of population spike firing in SD, an effect that was much reduced in GEPR. When SD slices were treated with bicuculline, a GABA(A) receptor antagonist, enhanced paired pulse facilitation and loss of inhibition during trains of stimuli were seen, similar to the patterns seen in GEPR. Previous studies in another brain area of GEPR, inferior colliculus, have shown loss of neuronal inhibition, and pharmacologic studies were consistent with reduced GABA-mediated inhibition. The present study suggests that abnormally reduced neuronal inhibition is also present in GEPR forebrain, and causes an exaggerated tendency to fire action potentials, which may be a significant factor in GEPR seizure predisposition.