Niittykoski M, Nissinen J, Penttonen M, Pitkänen A
Epilepsy Research Laboratory, Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.
Neuroscience. 2004;124(2):269-81. doi: 10.1016/j.neuroscience.2003.11.027.
The functional consequences of neuronal loss during epileptogenesis in the lateral and basal amygdaloid nuclei are poorly understood. The present study tested the hypothesis that electrical responsiveness varies in different amygdaloid nuclei in the chronically epileptic amygdala. Further, we examined the amygdaloid region most prone to seizure initiation. Epileptogenesis was triggered in 20 rats by inducing status epilepticus (SE) with electrical stimulation of the lateral nucleus of the amygdala. Electrode-implanted non-stimulated rats served as controls. The occurrence and duration of spontaneous seizures were monitored with video-electroencephalography (EEG) at 8-9 weeks after SE. Thereafter, animals were killed and extracellular recordings were made from slices of both amygdalas. In the lateral nucleus of epileptic animals, the frequency of spontaneous responses was reduced compared with controls (P < 0.05). The amplitudes of evoked field responses were reduced (P < 0.01), whereas paired pulse (PP) facilitation was enhanced (P < or = 0.05). In the basal nucleus of the epileptic animals, PP facilitation was enhanced (P < 0.05) and sensitivity to 4-aminopyridine (4-AP)-induced epileptiform activity was increased compared with controls (P < 0.05). In the epileptic animals, the basal nucleus was also more sensitive than the lateral nucleus to 4-AP-induced epileptiform activity (P < 0.05). Correlation analysis indicated that longer SE duration was associated with longer half widths (P = 0.001) and smaller slopes (P < 0.05) of evoked responses as well as with attenuated PP facilitation (P<0.01). Moreover, a higher frequency of spontaneous seizures was associated with longer half widths (P < 0.05) and smaller slopes (P < 0.05) of evoked responses as well as with enhanced PP facilitation (P < 0.05). These data suggest that there is a reduced release of glutamate and reduced inhibition in the lateral and basal amygdaloid nuclei in epileptic animals. Further, the basal nucleus is more prone to epileptic activity than the lateral nucleus. Finally, the severity of SE and spontaneous seizures in vivo is associated with electrophysiologic alterations in vitro.
外侧和基底杏仁核在癫痫发生过程中神经元丢失的功能后果目前还知之甚少。本研究验证了这样一个假说：在慢性癫痫杏仁核中，不同杏仁核的电反应性存在差异。此外，我们还研究了最易引发癫痫发作的杏仁核区域。通过电刺激杏仁核外侧核诱导癫痫持续状态（SE），在20只大鼠中引发癫痫发生。植入电极但未接受刺激的大鼠作为对照。在SE后8 - 9周，用视频脑电图（EEG）监测自发癫痫发作的发生和持续时间。此后，处死动物并从两侧杏仁核切片进行细胞外记录。在癫痫动物的外侧核中，与对照组相比，自发反应频率降低（P < 0.05）。诱发电场反应的幅度降低（P < 0.01），而双脉冲（PP）易化增强（P ≤ 0.05）。在癫痫动物的基底核中，PP易化增强（P < 0.05），与对照组相比，对4 - 氨基吡啶（4 - AP）诱导的癫痫样活动敏感性增加（P < 0.05）。在癫痫动物中，基底核对4 - AP诱导的癫痫样活动也比外侧核更敏感（P < 0.05）。相关性分析表明，SE持续时间越长，诱发电反应的半高宽越长（P = 0.001）、斜率越小（P < 0.05），PP易化减弱（P < 0.01）。此外，自发癫痫发作频率越高，诱发电反应的半高宽越长（P < 0.05）、斜率越小（P < 0.05），PP易化增强（P < 0.05）。这些数据表明，癫痫动物外侧和基底杏仁核中谷氨酸释放减少且抑制作用减弱。此外，基底核比外侧核更易发生癫痫活动。最后，体内SE和自发癫痫发作的严重程度与体外电生理改变相关。
