Aberrant GABA(A) receptor-mediated inhibition in cortico-thalamic networks of succinic semialdehyde dehydrogenase deficient mice.
Aberrant GABA(A) receptor-mediated inhibition in cortico-thalamic networks of succinic semialdehyde dehydrogenase deficient mice.
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DOI：
10.1371/journal.pone.0019021
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发表时间：
2011-04-19
期刊：
影响因子：
3.7
通讯作者：
Cope DW
中科院分区：
文献类型：
--
作者：
Errington AC;Gibson KM;Crunelli V;Cope DW
异常γ-氨基丁酸A型（GABAA）受体介导的抑制皮质-丘脑网络仍然是一个有吸引力的机制，典型的失神发作的发生。使用全细胞膜片钳技术，我们研究了“阶段性”和“紧张性”GABAA抑制的丘脑皮层神经元的躯体感觉（腹基底，VB）丘脑，丘脑网状核（NRT）神经元，和层5/6锥体神经元的躯体感觉（桶）皮层的琥珀酸半醛脱氢酶（SSADH）敲除（SSADH−/−）小鼠复制人类SSADH缺乏症，并表现出典型的失神发作。我们发现，与野生型动物相比，SSADH−/−小鼠VB和NRT神经元的sIPSC频率增加，VB神经元的sIPSC振幅更大，这表明SSADH−/−小鼠丘脑的总相位抑制增加。VB和NRT神经元中的mIPSC在基因型之间没有差异，尽管在SSADH−/−小鼠中仍然存在更多事件的趋势。在皮质层5/6锥体神经元中，SSADH−/−小鼠的sIPSC较少但较大，这是mIPSC保留的特征。与WT相比，SSADH−/−小鼠的丘脑皮质神经元和第5/6层锥体神经元的紧张性电流更大。这些数据表明，SSADH−/−小鼠的皮质-丘脑网络中GABAA受体介导的抑制作用增强，而不是减弱。与以前的研究一致，GABAA受体介导的抑制性功能获得可能是典型失神发作模型的共同特征，并且可能在SSADH缺乏症患者中具有病理重要性。
Aberrant γ-aminobutyric acid type A (GABAA) receptor-mediated inhibition in cortico-thalamic networks remains an attractive mechanism for typical absence seizure genesis. Using the whole-cell patch clamp technique we examined ‘phasic’ and ‘tonic’ GABAA inhibition in thalamocortical neurons of somatosensory (ventrobasal, VB) thalamus, nucleus reticularis thalami (NRT) neurons, and layer 5/6 pyramidal neurons of the somatosensory (barrel) cortex of succinic semialdehyde dehydrogenase (SSADH) knock-out (SSADH−/−) mice that replicate human SSADH deficiency and exhibit typical absence seizures. We found increased sIPSC frequency in both VB and NRT neurons and larger sIPSC amplitude in VB neurons of SSADH−/− mice compared to wild-type animals, demonstrating an increase in total phasic inhibition in thalamus of SSADH−/− mice. mIPSCs in both VB and NRT neurons were no different between genotypes, although there remained a trend toward more events in SSADH−/− mice. In cortical layer 5/6 pyramidal neurons, sIPSCs were fewer but larger in SSADH−/− mice, a feature retained by mIPSCs. Tonic currents were larger in both thalamocortical neurons and layer 5/6 pyramidal neurons from SSADH−/− mice compared to WTs. These data show that enhanced, rather than compromised, GABAA receptor-mediated inhibition occurs in cortico-thalamic networks of SSADH−/− mice. In agreement with previous studies, GABAA receptor-mediated inhibitory gain-of-function may be a common feature in models of typical absence seizures, and could be of pathological importance in patients with SSADH deficiency.
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影响因子：
82.9
作者：
Cope, David W.;Di Giovanni, Giuseppe;Fyson, Sarah J.;Orban, Gergely;Errington, Adam C.;Lorincz, Magor L.;Gould, Timothy M.;Carter, David A.;Crunelli, Vincenzo
通讯作者：
Crunelli, Vincenzo
影响因子：
5.6
作者：
Blumenfeld, H
通讯作者：
Blumenfeld, H
影响因子：
2.5
作者：
Bessaih, Thomas;Bourgeais, Laurence;Leresche, Nathalie
通讯作者：
Leresche, Nathalie
影响因子：
2.2
作者：
Hosford, DA;Wang, Y;Cao, Z
通讯作者：
Cao, Z
影响因子：
4.2
作者：
Drasbek, K. R.;Vardya, I.;Delenclos, M.;Gibson, K. M.;Jensen, K.
通讯作者：
Jensen, K.