Recurrent excitatory connectivity in the dentate gyrus of kindled and kainic acid-treated rats
Recurrent excitatory connectivity in the dentate gyrus of kindled and kainic acid-treated rats
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DOI：
10.1152/jn.2000.83.2.693
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发表时间：
2000-02-01
影响因子：
2.5
通讯作者：
Sutula, T
中科院分区：
文献类型：
--
作者：
Lynch, M;Sutula, T
反复发作诱导苔藓纤维轴突发芽，重组齿状回的突触连接。为了研究发芽苔藓纤维轴突可能形成反复兴奋回路的可能性，在正常大鼠和癫痫大鼠的横向海马切片中检查了齿状回颗粒细胞之间的连接，癫痫大鼠经历了点燃和红藻氨酸诱导的癫痫发作。实验的目的是功能性评估癫痫诱导的发展，通过利用点燃模型中癫痫诱导的突触重组的时间过程和红藻氨酸模型中发芽纤维的详细解剖特征的信息。当GABA、受体拮抗剂荷包牡丹碱阻断复发性抑制回路时，在远离记录的颗粒细胞的颗粒细胞层中局部应用谷氨酸微滴诱发癫痫大鼠的兴奋性突触后电位（EPSP）和群体爆发性放电，这在正常大鼠脑片中从未观察到。的EPSPs和爆发式放电被阻止浴应用1 μ M河豚毒素，因此依赖于网络驱动的突触事件。在海人酸诱导的癫痫持续状态大鼠海马脑片中，在齿状回叶片之间检测到兴奋性连接。列车的EPSPs和爆发式放电也诱发颗粒细胞点燃大鼠点燃后获得大于或等于1周的点燃癫痫发作，但没有诱发切片检查后24小时，发芽的发展之前，一个单一的后放电。齿状回叶片之间的兴奋性连接也进行了评估，在切片通过横断的穿通路径，并浸泡在人工脑脊液（ACSF）含有荷包牡丹碱阻断GABA，受体依赖性复发抑制电路和10 mM [Ca 2 +]（o）抑制多突触活动。在这些条件下，低强度电刺激的锥体下叶未能引起正常大鼠（n = 15）的上锥体颗粒细胞的反应，但在切片癫痫大鼠诱发的EPSP在短潜伏期（2.59 +/- 0.36 ms）在5的18个上锥体颗粒细胞。这一结果与齿状回叶片间单突触兴奋性连接的形成是一致的。癫痫大鼠的齿状回中出现了与苔藓纤维发芽的发展相对应的周期性兴奋回路，并表现出功能连接的模式：对应于发芽苔藓纤维通路的解剖特征。
Repeated seizures induce mossy fiber axon sprouting, which reorganizes synaptic connectivity in the dentate gyrus. To examine the possibility that sprouted mossy fiber axons may form recurrent excitatory circuits, connectivity between granule cells in the dentate gyrus was examined in transverse hippocampal slices from normal rats and epileptic rats that experienced seizures induced by kindling and kainic acid. The experiments were designed to functionally assess seizure-induced development of recurrent circuitry by exploiting information available about the time course of Seizure-induced synaptic reorganization in the kindling model and detailed anatomic characterization of sprouted fibers in the kainic acid model. When recurrent inhibitory circuits were blocked by the GABA, receptor antagonist bicuculline, focal application of glutamate microdrops at locations in the granule cell layer remote from the recorded granule cell evoked trains of excitatory postsynaptic potentials (EPSPs) and population burst discharges in epileptic rats, which were never observed in slices from normal rats. The EPSPs and burst discharges were blocked by bath application of 1 mu M tetrodotoxin and were therefore dependent on network-driven synaptic events. Excitatory connections were detected between blades of the dentate gyrus in hippocampal slices from rats that experienced kainic acid-induced status epilepticus. Trains of EPSPs and burst discharges were also evoked in granule cells from kindled rats obtained after greater than or equal to 1 wk of kindled seizures, but were not evoked in slices examined 24 h after a single afterdischarge, before the development of sprouting. Excitatory connectivity between blades of the dentate gyrus was also assessed in slices deafferented by transection of the perforant path, and bathed in artificial cerebrospinal fluid (ACSF) containing bicuculline to block GABA, receptor-dependent recurrent inhibitory circuits and 10 mM [Ca2+](o) to suppress polysynaptic activity. Low-intensity electrical stimulation of the infrapyramidal blade under these conditions failed to evoke a response in suprapyramidal granule cells from normal rats (n = 15), but in slices from epileptic rats evoked an EPSP at a short latency (2.59 +/- 0.36 ms) in 5 of 18 suprapyramidal granule cells. The results are consistent with formation of monosynaptic excitatory connections between blades of the dentate gyrus. Recurrent excitatory circuits developed in the dentate gyrus of epileptic rats in a rime course that corresponded to the development of mossy fiber sprouting and demonstrated patterns of functional connectivity: corresponding to anatomic features of the sprouted mossy fiber pathway.