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颞叶癫痫慢性模型中CA1区和齿状回兴奋性神经传递的变化。

Changes in excitatory neurotransmission in the CA1 region and dentate gyrus in a chronic model of temporal lobe epilepsy.

作者信息

Lothman E W, Rempe D A, Mangan P S

机构信息

Department of Neurology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.

出版信息

J Neurophysiol. 1995 Aug;74(2):841-8. doi: 10.1152/jn.1995.74.2.841.

DOI:10.1152/jn.1995.74.2.841
PMID:7472387
Abstract
  1. In this report we compare changes of excitatory neurotransmission within the CA1 region and the dentate gyrus (DG) in a model of chronic temporal lobe epilepsy (TLE). Extracellular and intracellular recordings were obtained from in vitro hippocampal-parahippocampal slices > or = 1 mo after a period of self-sustaining limbic status epilepticus (SSLSE) induced by continuous hippocampal stimulation. Pyramidal cells in CA1 were activated by electrodes in the stratum lacunosum/moleculare or stratum radiatum. Granule cells in DG were similarly activated by electrodes positioned in the perforant path. 2. Monosynaptic excitatory postsynaptic potentials (EPSPs) evoked in CA1 pyramidal cells in post-SSLSE tissue were always longer than those evoked in control tissue, irrespective of whether hyperresponsiveness was present or not. EPSPs elicited by stimulus subthreshold for action potentials (APs) in post-SSLSE and in control slices and matched in amplitude had a statistically greater duration in the post-SSLSE slices. Durations of monosynaptic EPSPs elicited by stimuli subthreshold for APs in DG granule cells in post-SSLSE slices were not longer than EPSPs of equal amplitude elicited in control slices. 3. Higher-intensity stimuli produced EPSPs with associated APs and, in certain cases in the post-SSLSE tissue, hyperresponsive events with multiple (> or = 3) APs. Durations of depolarizing profiles with stimuli producing APs were overall longer in both CA1 pyramidal cells and DG granule cells and correlated with the degree of hyperresponsiveness. 4. Neither the amplitudes nor the durations of monosynaptic EPSPs evoked in CA1 pyramidal cells in slices from control animals were affected by the addition of D(-)-2-amino-5-phosphonovaleric acid (APV), a blocker of the N-methyl-D-aspartate (NMDA) receptor, to the artificial cerebrospinal fluid (ACSF) bathing the slices. In contrast to the situation in control tissue, in post-SSLSE tissue APV shortened EPSPs evoked in CA1 pyramidal cells while not changing their amplitudes. After APV, inhibitory postsynaptic potentials (IPSPs) remained greatly diminished or absent in CA1 pyramidal cells. APV did not statistically decrease amplitudes of monosynaptic EPSPs evoked in DG granule cells in either control slices or post-SSLSE slices. APV decreased EPSP durations in both types of slices, more so in the post-SSLSE tissue. 5. In control slices, APV did not change the amplitudes or durations of depolarizing profiles of responses evoked by stimuli producing APs in CA1. Similarly, APV did not change the amplitudes of such responses in DG. However, APV did reduce the durations of such responses in DG in control slices.(ABSTRACT TRUNCATED AT 400 WORDS)
摘要
  1. 在本报告中,我们比较了慢性颞叶癫痫(TLE)模型中CA1区和齿状回(DG)内兴奋性神经传递的变化。在通过持续海马刺激诱导的自维持边缘性癫痫持续状态(SSLSE)持续1个月或更长时间后,从体外海马-海马旁回切片中获得细胞外和细胞内记录。CA1区的锥体细胞由分子层/腔隙层或放射层中的电极激活。DG中的颗粒细胞同样由位于穿通路径中的电极激活。2. SSLSE后组织中CA1锥体细胞诱发的单突触兴奋性突触后电位(EPSP)总是比对照组织中诱发的EPSP长,无论是否存在高反应性。在SSLSE后切片和对照切片中,由低于动作电位(AP)阈值的刺激诱发且幅度匹配的EPSP,在SSLSE后切片中的持续时间在统计学上更长。SSLSE后切片中DG颗粒细胞由低于AP阈值的刺激诱发的单突触EPSP的持续时间,并不比对照切片中诱发的等幅EPSP长。3. 高强度刺激产生伴有AP的EPSP,并且在某些情况下,在SSLSE后组织中产生具有多个(≥3个)AP的高反应性事件。在CA1锥体细胞和DG颗粒细胞中,产生AP的刺激引起的去极化波形的持续时间总体上更长,并且与高反应性程度相关。4. 向浸泡切片的人工脑脊液(ACSF)中添加N-甲基-D-天冬氨酸(NMDA)受体阻滞剂D-(-)-2-氨基-5-磷酸戊酸(APV),对对照动物切片中CA1锥体细胞诱发的单突触EPSP的幅度和持续时间均无影响。与对照组织中的情况相反,在SSLSE后组织中,APV缩短了CA1锥体细胞诱发的EPSP,而不改变其幅度。加入APV后,CA1锥体细胞中的抑制性突触后电位(IPSP)仍然大大减弱或消失。APV在统计学上并未降低对照切片或SSLSE后切片中DG颗粒细胞诱发的单突触EPSP的幅度。APV在两种类型的切片中均降低了EPSP持续时间,在SSLSE后组织中降低得更多。5. 在对照切片中,APV不改变CA1中由产生AP的刺激诱发的反应的去极化波形的幅度或持续时间。同样,APV不改变DG中此类反应的幅度。然而,APV确实降低了对照切片中DG中此类反应的持续时间。(摘要截短为400字)

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