NONSYNAPTIC EPILEPTOGENESIS IN THE MAMMALIAN HIPPOCAMPUS INVITRO .1. DEVELOPMENT OF SEIZURE-LIKE ACTIVITY IN LOW EXTRACELLULAR CALCIUM
NONSYNAPTIC EPILEPTOGENESIS IN THE MAMMALIAN HIPPOCAMPUS INVITRO .1. DEVELOPMENT OF SEIZURE-LIKE ACTIVITY IN LOW EXTRACELLULAR CALCIUM
复制标题
DOI：
10.1152/jn.1986.56.2.409
复制
发表时间：
1986-08-01
影响因子：
2.5
通讯作者：
YAARI, Y
中科院分区：
文献类型：
--
作者：
KONNERTH, A;HEINEMANN, U;YAARI, Y
通过细胞外和细胞内记录研究了通过降低细胞外 Ca2+ 浓度 ([Ca2+]o) 在大鼠海马切片中诱导的癫痫样活动。用低 Ca2+（小于或等于 0.2 mM）或含有 EGTA 的溶液灌注切片会阻断海马锥体细胞 (HPC) 的突触反应。尽管存在阻滞，CA1 区域仍出现自发性发作，称为癫痫样事件 (SLE)，然后以稳定的频率定期复发。短暂的缺氧加速了它们的发育并增加了它们的频率。当[Ca2+]o逐步升高时，SLE在0.3 mM时消失。通过 CA1 锥体层的细胞外记录，SLE 的特征是场电位出现大幅负移，持续数秒。在此期间，大量的 CA1 神经元强烈且经常同步放电，正如群体峰值的频繁出现所得出的结论。然而，同步并不是阵发性活动发展的必要先兆，而似乎是大量神经元兴奋的最终结果。根据发作放电区 HPC 的细胞内记录显示，SLE 的细胞对应物是高达 20 mV 的持久去极化位移 (LDS)。这伴随着神经元的加速放电。每个 LDS 都会发生长时间的后超极化，并阻止细胞放电。 LDS 发作前通常会观察到短暂（约 50 ms）的爆发。局部施加于锥体层或肺泡的单次电刺激会引起与自发性 SLE 相同的阵发，前提是它们超过了临界阈值强度。阈下刺激仅引起较小的局部反应，而不同阈上强度的刺激引起相同的最大SLE。因此，SLE 的形成是一个全有或全无或再生过程，它动员了大多数（如果不是全部）局部神经元群。每个 SLE 之后都有绝对和相对不应期，在此期间，局灶性刺激在诱发最大 SLE 方面分别无效和不太有效。在大多数切片中，自发性 SLE 始于位于 CA1a 分区（靠近下托）的“焦点”。由局部刺激引起的系统性红斑狼疮出现在刺激电极附近。阵发性放电从其起源部位以 1.74 mm/s 的平均速度横向传播到整个 CA1 区域。因此，SLE 的放电区域可能会在几秒钟内覆盖整个 CA1 区域。（摘要截断为 400 字）
Epileptiform activity induced in rat hippocampal slices by lowering extracellular Ca2+ concentration ([Ca2+]o) was studied with extracellular and intracellular recordings. Perfusing the slices with low Ca2+ (less than or equal to 0.2 mM) or EGTA-containing solutions blocked the synaptic responses of hippocampal pyramidal cells (HPCs). Despite the block, spontaneous paroxysms, termed seizurelike events (SLEs), appeared in the CA1 area and then recurred regularly at a stable frequency. Transient hypoxia accelerated their development and increased their frequency. When [Ca2+]o was raised in a stepwise manner, the SLEs disappeared at 0.3 mM. With extracellular recording from the CA1 stratum pyramidale, a SLE was characterized by a large negative shift in the field potential, which lasted for several seconds. During this period a large population of CA1 neurons discharged intensely and often in synchrony, as concluded from the frequent appearance of population spikes. Synchronization, however, was not a necessary precursor for the development of paroxysmal activity, but seemed to be the end result of massive neuronal excitation. The cellular counterpart of a SLE, as revealed by intracellular recording from HPCs in the discharge zone of the paroxysms, was a long-lasting depolarization shift (LDS) of up to 20 mV. This was accompanied by accelerated firing of the neuron. A prolonged after-hyperpolarization succeeded each LDS and arrested cell firing. Brief (approximately 50 ms) bursts were commonly observed before LDS onset. Single electrical stimuli applied focally to the stratum pyramidale or alveus evoked paroxysms identical to the spontaneous SLEs, provided they surpassed a critical threshold intensity. Subthreshold stimuli elicited only small local responses, whereas stimuli of varied suprathreshold intensities evoked the same maximal SLEs. Thus the buildup of a SLE is an all or nothing or a regenerative process, which mobilizes the majority, if not all, of the local neuronal population. Each SLE was followed by absolute and relative refractory periods during which focal stimulation was, respectively, ineffective and less effective in evoking a maximal SLE. In most slices the spontaneous SLEs commenced at a "focus" located in the CA1a subarea (near the subiculum). SLEs evoked by focal stimulation arose near the stimulating electrode. From their site of origin the paroxysmal discharges spread transversely through the entire CA1 area at a mean velocity of 1.74 mm/s. Consequently, the discharge zone of a SLE could encompass for several seconds the entire CA1 area.(ABSTRACT TRUNCATED AT 400 WORDS)