Vulnerability of cholecystokinin-expressing GABAergic interneurons in the unilateral intrahippocampal kainate mouse model of temporal lobe epilepsy.
Vulnerability of cholecystokinin-expressing GABAergic interneurons in the unilateral intrahippocampal kainate mouse model of temporal lobe epilepsy.
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DOI：
10.1016/j.expneurol.2021.113724
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发表时间：
2021-08
影响因子：
5.3
通讯作者：
Lee SH
中科院分区：
文献类型：
--
作者：
Kang YJ;Clement EM;Park IH;Greenfield LJ Jr;Smith BN;Lee SH
颞叶癫痫（TLE）的特征是反复自发性癫痫发作和行为合并症。海马θ振荡减少和过度兴奋，导致认知缺陷和自发性癫痫发作，目前超出了颞叶癫痫患者的score-hippocampus。然而，在远离硬化海马的回路中观察到的网络振荡受损和过度兴奋的潜在机制在很大程度上尚不清楚。表达胆囊收缩素（CCK）的篮状细胞（CCKBC）参与海马Theta节律的形成，并调节神经元的兴奋性。因此，我们研究是否CCKBCs是脆弱的腹侧海马nonsclerotic区域远离背侧sclerotic海马使用海马内红藻氨酸（IHK）小鼠模型TLE，针对单侧背侧海马。我们发现，减少CCK+中间神经元的数量在同侧腹侧CA 1区癫痫小鼠相比，那些从假对照。我们还发现，CCK+中间神经元的扣结的数量减少，但在其他CA 1层，癫痫小鼠同侧海马，这表明CCKBCs是脆弱的。电记录显示，从存活的CCKBC到CA 1锥体细胞（PC）的突触连接和强度在癫痫小鼠和假手术对照组之间是相似的。与TLE中CCKBC数量减少一致，电记录显示癫痫小鼠腹侧CA 1区卡巴胆碱（通常用于激发CCK+中间神经元）诱发的CA 1 PC中IPSC的振幅和频率显著降低。这些结果表明，超出海马病变的CCKBC的损失可能有助于TLE的过度兴奋和受损的网络振荡。
Temporal lobe epilepsy (TLE) is characterized by recurrent spontaneous seizures and behavioral comorbidities. Reduced hippocampal theta oscillations and hyperexcitability that contribute to cognitive deficits and spontaneous seizures are present beyond the sclerotic hippocampus in TLE. However, the mechanisms underlying compromised network oscillations and hyperexcitability observed in circuits remote from the sclerotic hippocampus are largely unknown. Cholecystokinin (CCK)-expressing basket cells (CCKBCs) critically participate in hippocampal theta rhythmogenesis, and regulate neuronal excitability. Thus, we examined whether CCKBCs were vulnerable in nonsclerotic regions of the ventral hippocampus remote from dorsal sclerotic hippocampus using the intrahippocampal kainate (IHK) mouse model of TLE, targeting unilateral dorsal hippocampus. We found a decrease in the number of CCK+ interneurons in ipsilateral ventral CA1 regions from epileptic mice compared to those from sham controls. We also found that the number of boutons from CCK+ interneurons was reduced in the stratum pyramidale, but not in other CA1 layers, of ipsilateral hippocampus in epileptic mice, suggesting that CCKBCs are vulnerable. Electrical recordings showed that synaptic connectivity and strength from surviving CCKBCs to CA1 pyramidal cells (PCs) were similar between epileptic mice and sham controls. In agreement with reduced CCKBC number in TLE, electrical recordings revealed a significant reduction in amplitude and frequency of IPSCs in CA1 PCs evoked by carbachol (commonly used to excite CCK+ interneurons) in ventral CA1 regions from epileptic mice versus sham controls. These findings suggest that loss of CCKBCs beyond the hippocampal lesion may contribute to hyperexcitability and compromised network oscillations in TLE.
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影响因子：
2.5
作者：
Dinocourt, C;Petanjek, Z;Esclapez, M
通讯作者：
Esclapez, M
影响因子：
3.5
作者：
Armstrong C;Wang J;Yeun Lee S;Broderick J;Bezaire MJ;Lee SH;Soltesz I
通讯作者：
Soltesz I
影响因子：
3.7
作者：
Alger BE;Nagode DA;Tang AH
通讯作者：
Tang AH
影响因子：
2.6
作者：
Canovas, Rosa;Leon, Irene;Manuel Cimadevilla, Jose
通讯作者：
Manuel Cimadevilla, Jose
影响因子：
7.7
作者：
Bezaire, Marianne J.;Raikov, Ivan;Soltesz, Ivan
通讯作者：
Soltesz, Ivan