Klueva Julia, Munsch Thomas, Albrecht Doris, Pape Hans-Christian
Institut für Physiologie, Medizinische Fakultät, Otto-von-Guericke-Universität Magdeburg, D-39120 Magdeburg, Germany.
Eur J Neurosci. 2003 Nov;18(10):2779-91. doi: 10.1111/j.1460-9568.2003.02984.x.
Lateral amygdala (LA) activity during synchronized-epileptiform discharges in temporolimbic circuits was investigated in rat horizontal slices containing the amygdala, hippocampus (Hip), perirhinal (Prh) and lateral entorhinal (LEnt) cortex, through multiple-site extra- and intracellular recording techniques and measurement of the extracellular K+ concentration. Application of 4-aminopyridine (50 microm) induced epileptiform discharges in all regions under study. Slow interictal-like burst discharges persisted in the Prh/LEnt/LA after disconnection of the Hip, seemed to originate in the Prh as shown from time delay analyses, and often preceded the onset of ictal-like activity. Disconnection of the amygdala resulted in de-synchronization of epileptiform discharges in the LA from those in the Prh/LEnt. Interictal-like activity was intracellularly reflected in LA projection neurons as gamma-aminobutyric acid (GABA)A/B receptor-mediated synaptic responses, and depolarizing electrogenic events (spikelets) residing on the initial phase of the GABA response. Spikelets were considered antidromically conducted ectopic action potentials generated at axon terminals, as they were graded in amplitude, were not abolished through hyperpolarizing membrane responses (which effectively blocked evoked orthodromic action potentials), lacked a clear prepotential or synaptic potential, were not affected through blockers of gap junctions, and were blocked through remote application of tetrodotoxin at putative target areas of LA projection neurons. Remote application of a GABAB receptor antagonist facilitated spikelet generation. A transient elevation in the extracellular K+ level averaging 3 mm above baseline occurred in conjunction with interictal-like activity in all areas under study. We conclude that interictal-like discharges in the LA/LEnt/Prh spread in a predictable manner through the synaptic network with the Prh playing a leading role. The rise in extracellular K+ may provide a depolarizing mechanism for recruitment of interneurons and generation of ectopic action potentials at axon terminals of LA projection neurons. Antidromically conducted ectopic action potentials may provide a spreading mechanism of seizure activity mediated by diffuse axonal projections of LA neurons.
通过多位点细胞外和细胞内记录技术以及细胞外钾离子浓度测量，在包含杏仁核、海马体（Hip）、内嗅周皮质（Prh）和外侧内嗅皮质（LEnt）的大鼠水平切片中，研究了颞叶边缘回路同步癫痫样放电期间外侧杏仁核（LA）的活动。应用4-氨基吡啶（50微摩尔）可在所有研究区域诱发癫痫样放电。海马体切断后，Prh/LEnt/LA中持续存在缓慢的发作间期样爆发放电，从时间延迟分析来看，似乎起源于Prh，并且常常先于发作样活动的开始。杏仁核切断导致LA中癫痫样放电与Prh/LEnt中的放电不同步。发作间期样活动在LA投射神经元中通过γ-氨基丁酸（GABA）A/B受体介导的突触反应以及位于GABA反应初始阶段的去极化电活动事件（小棘波）在细胞内得到反映。小棘波被认为是在轴突末端产生的逆向传导异位动作电位，因为它们的幅度是分级的，不会通过超极化膜反应而消除（超极化膜反应可有效阻断诱发的顺向动作电位），缺乏明显的预电位或突触电位，不受缝隙连接阻滞剂的影响，并且在LA投射神经元的假定靶区域通过远程应用河豚毒素而被阻断。远程应用GABAB受体拮抗剂促进了小棘波的产生。在所有研究区域，细胞外钾离子水平平均比基线升高3毫米的短暂升高与发作间期样活动同时出现。我们得出结论，LA/LEnt/Prh中的发作间期样放电通过突触网络以可预测的方式传播，其中Prh起主导作用。细胞外钾离子的升高可能为中间神经元的募集以及LA投射神经元轴突末端异位动作电位的产生提供去极化机制。逆向传导的异位动作电位可能为由LA神经元的弥散轴突投射介导的癫痫活动提供传播机制。
