Contributions of mossy fiber and CA1 pyramidal cell sprouting to dentate granule cell hyperexcitability in kainic acid-treated hippocampal slice cultures
Contributions of mossy fiber and CA1 pyramidal cell sprouting to dentate granule cell hyperexcitability in kainic acid-treated hippocampal slice cultures
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DOI：
10.1152/jn.01028.2003
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发表时间：
2004-12-01
影响因子：
2.5
通讯作者：
McNamara, JO
中科院分区：
文献类型：
--
作者：
Bausch, SB;McNamara, JO
像苔藓状纤维一样的轴突发芽通常与颞叶癫痫有关，但其意义尚不清楚。为了研究苔藓纤维发芽的功能后果和替代途径，在海马体切片培养中使用kainic酸（KA）诱导强健的苔藓纤维发芽。生理比较记录了KA-和载体处理的培养物之间颗粒细胞反应的许多相似之处，包括：癫痫发作，癫痫样爆发和自发兴奋突触后电流（sEPSCs） bb0 600pA。gaba能的控制和谷氨酸能突触传递的贡献相似。对充满神经生物素的CA1锥体细胞的分析显示，在载体和KA处理的培养物中，轴突发芽都很强劲，KA处理的培养物中，轴突发芽明显更大。在对照和ka处理的培养物中，Hilar刺激引起了一个反向的种群峰值，随后是可变数量的突触后电位（psp）和种群峰值。尽管有强健的苔状纤维发芽，但刀切将CA1与齿状回分离，实际上消除了KA处理的培养物中由门部刺激引起的epsp，而不是用培养液处理的培养物，这表明在KA处理的培养物中，从CA1到齿状回的功能性传入信号起着关键作用。总之，这些发现表明，在长期海马切片培养中，用载药或KA处理后，齿状颗粒细胞具有惊人的高兴奋性。在ka处理的培养物中，意想不到的轴突从CA1到齿状突起对颗粒细胞hila诱发的高兴奋性的贡献强化了轴突发芽可能有助于颗粒细胞病理高兴奋性的观点。
Axonal sprouting like that of the mossy fibers is commonly associated with temporal lobe epilepsy, but its significance remains uncertain. To investigate the functional consequences of sprouting of mossy fibers and alternative pathways, kainic acid (KA) was used to induce robust mossy fiber sprouting in hippocampal slice cultures. Physiological comparisons documented many similarities in granule cell responses between KA- and vehicle-treated cultures, including: seizures, epileptiform bursts, and spontaneous excitatoty postsynaptic currents (sEPSCs) >600pA. GABAergic control and contribution of glutamatergic synaptic transmission were similar. Analyses of neurobiotin-filled CA1 pyramidal cells revealed robust axonal sprouting in both vehicle- and KA-treated cultures, which was significantly greater in KA- treated cultures. Hilar stimulation evoked an antidromic population spike followed by variable numbers of postsynaptic potentials (PSPs) and population spikes in both vehicle- and KA-treated cultures. Despite robust mossy fiber sprouting, knife cuts separating CA1 from dentate gyrus virtually abolished EPSPs evoked by hilar stimulation in KA-treated but not vehicle- treated cultures, suggesting a pivotal role of functional afferents from CA1 to dentate gyrus in KA- treated cultures. Together, these findings demonstrate striking hyperexcitability of dentate granule cells in long-term hippocampal slice cultures after treatment with either vehicle or KA. The contribution to hilar-evoked hyperexcitability of granule cells by the unexpected axonal projection from CA1 to dentate in KA-treated cultures reinforces the idea that axonal sprouting may contribute to pathologic hyperexcitability of granule cells.